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The wheels on the bus take lung cancer screening to rural areas
Results from a pilot study, published online July 13 in The Annals of Thoracic Surgery, show that the scheme is both practical and financially sustainable.
During a 10-month test run, the mobile unit screened 548 individuals at 104 sites. Five lung cancers (four of which were early stage) and a type B thymoma were discovered, and all of these individuals went on to have treatment.
Significant pulmonary findings were also discovered in 52 individuals, who were advised to undergo further testing, as well as significant nonpulmonary findings in 152 individuals (of whom 13 required further testing, but none went on to have treatment). These findings included severe coronary disease and thyroid abnormalities.
The bus reached the estimated financial break-even point of 428 scans, but future economic viability of such a program will likely rely on additional revenue from the treatment of patients with incidental findings from low-dose CT screens, acknowledged the authors, led by James R. Headrick Jr, MD, MBA, from the University of Tennessee College of Medicine in Chattanooga.
The real value of the Breathe Easy program, however, comes from bringing both patient education and lung cancer screening services to a high-risk population who might otherwise be overlooked, Headrick said in an interview with Medscape Medical News.
“We were all excited when lung screening was approved, and we got the recommendation from the United States Preventive Services Task Force [USPSTF], and the Centers for Medicare & Medicaid Services signed off on it, and we sat in our offices and clinics and hospitals — and nobody showed up. We were thinking, ‘Wow, we have this simple test, the easiest screening tool in the world, and nobody’s coming,’ “ he said.
“There was certainly an educational issue that needed to be solved,” he continued, “but we were also dealing with a population that had been told that if they smoked and didn’t live life well, there was a 100% chance they were going to get lung cancer and die,” he said.
The individuals screened in the program were very heavy smokers.
The mean pack-years of smoking was 41 — 11 pack-years higher than the minimum recommended under current lung cancer screening guidelines, and 21 pack-years higher than that recently recommended under proposed low-dose CT screening guidelines by the USPSTF.
Albert Rizzo, MD, chief medical officer for the American Lung Association, who was not involved in the study, told Medscape Medical News any initiative that can expand lung cancer screening is welcome, particularly when a program may be self-sustaining.
“The interesting part of this article included the downstream revenue to help make something like this viable,” Rizzo said. “Just doing the scans is probably not going to cover the cost of the mobile unit itself, but if you take into account that other things are being found in addition to lung cancer, such as coronary abnormalities, then it becomes more cost-effective, especially if those patients are then treated at the site where the mobile unit is coming from,” he said.
Starting at square one
The first mobile CT scanner was launched in Nagano Prefecture, a rural area in Japan, in 1996. Since then, mobile screening units, primarily mounted on tractor trailers, have brought screening to centralized areas, such as shopping mall parking lots. The Levine Cancer Institute in Charlotte, North Carolina, also has a mobile CT-screening unit mounted in a modified box truck.
For Headrick and colleagues the goal was not to reinvent the wheel, but to see if a mobile lung cancer screening program could improve access and also pay for itself in a time of parsimonious support for preventive medicine.
Their first challenge was the mobile unit itself.
“CT scanners are sensitive, complex electrical machines that require climate control and a level environment to operate. Historically, they have been placed in tractor trailers and parked on level concrete slabs connected to external power supplies. We needed mobility, self-leveling, independent power, climate control, patient comfort, and drivability,” they wrote.
They assembled a team of engineers from CT and vehicle makers, and input was also provided by a thoracic surgeon, pulmonologist, radiologist, CT technician, and driver with a commercial driver’s license. Together, they designed and built the bus over 8 months. Funds for the total cost of the prototype vehicle ($650,000) came from two local nonprofit foundations. The estimated cost for a commercial version of the same vehicle was $850,000.
The Breathe Easy pilot began operation in early 2018, with the initial plan to drive the bus within a 2-hour radius of CHI Memorial Hospital, Chattanooga, Tennessee, to avoid overnight trips. The radius was later shortened to 1.5 hours when operators realized it was a burden for patients with significant screening findings to travel to as much as 4 hours (round trip) to Chattanooga for further testing.
Each screening visit takes about 15 minutes.
Cancer and other significant findings
As noted before, the bus traveled to 104 sites over 10 months, and 548 patients with a mean age of 62 were screened. Five lung cancers were identified, including two stage 1A, one stage 1A2, one stage 1B, and one stage 3A.
Two patients with early stage disease underwent stereotactic body radiation therapy, and two underwent minimally invasive surgery (a segmentectomy and a lobectomy). The patient with stage 3A disease underwent curative chemotherapy and radiation therapy. One patient with a type B1 thymoma underwent robotic-assisted thoracoscopic resection with en bloc pericardial resection and reconstruction.
A total of 51 patients had a significant pulmonary finding of Lung CT Screening Reporting and Data System (Lung-RADS) 3 or 4 and were advised to follow up with further testing, but 17 patients in this group did not pursue further testing. Of these 17 patients, 15 had been screened in a health clinic for the homeless at a rural site.
Significant nonpulmonary findings included moderate to severe coronary artery disease in 101 patients, abdominal findings in 15, thyroid abnormalities in 14, other thoracic findings in 10, and ascending aortic dilatation in 9. Of the 152 patients with nonpulmonary findings, only 13 required further testing and none required treatment.
Revisions, improvements, and priorities
The Breathe Easy bus has been in operation for more than 2 years, performing an average of approximately 100 screenings per month, with a goal of 200. The bus continued to operate throughout the COVID-19 pandemic because many patients viewed it as a safer alternative to a hospital visit, Headrick said.
Design changes planned to improve performance of the bus include a stronger chassis and structural components, as well as swapping out the 16-slice CT unit for a specially designed 64-slice mobile unit that can be operated with an iPad and provide gated coronary calcium scores.
When challenged about whether the cost of lung cancer screening is the best use of limited resources, Headrick said, “if it’s not, then when we need to go back to the drawing board and jump-start lung cancer screening.”
“When I spent a year in 2014-2015 trying to talk to radio stations, news stations, media, nobody really cared about lung cancer screening,” he said. “But as soon as I had this shiny object, which is the bus, which we labeled as the easiest and most valuable doctor visit, people had an interest.”
The pilot study was supported by local nonprofit foundations through the CHI Memorial Foundation.
This article first appeared on Medscape.com.
Results from a pilot study, published online July 13 in The Annals of Thoracic Surgery, show that the scheme is both practical and financially sustainable.
During a 10-month test run, the mobile unit screened 548 individuals at 104 sites. Five lung cancers (four of which were early stage) and a type B thymoma were discovered, and all of these individuals went on to have treatment.
Significant pulmonary findings were also discovered in 52 individuals, who were advised to undergo further testing, as well as significant nonpulmonary findings in 152 individuals (of whom 13 required further testing, but none went on to have treatment). These findings included severe coronary disease and thyroid abnormalities.
The bus reached the estimated financial break-even point of 428 scans, but future economic viability of such a program will likely rely on additional revenue from the treatment of patients with incidental findings from low-dose CT screens, acknowledged the authors, led by James R. Headrick Jr, MD, MBA, from the University of Tennessee College of Medicine in Chattanooga.
The real value of the Breathe Easy program, however, comes from bringing both patient education and lung cancer screening services to a high-risk population who might otherwise be overlooked, Headrick said in an interview with Medscape Medical News.
“We were all excited when lung screening was approved, and we got the recommendation from the United States Preventive Services Task Force [USPSTF], and the Centers for Medicare & Medicaid Services signed off on it, and we sat in our offices and clinics and hospitals — and nobody showed up. We were thinking, ‘Wow, we have this simple test, the easiest screening tool in the world, and nobody’s coming,’ “ he said.
“There was certainly an educational issue that needed to be solved,” he continued, “but we were also dealing with a population that had been told that if they smoked and didn’t live life well, there was a 100% chance they were going to get lung cancer and die,” he said.
The individuals screened in the program were very heavy smokers.
The mean pack-years of smoking was 41 — 11 pack-years higher than the minimum recommended under current lung cancer screening guidelines, and 21 pack-years higher than that recently recommended under proposed low-dose CT screening guidelines by the USPSTF.
Albert Rizzo, MD, chief medical officer for the American Lung Association, who was not involved in the study, told Medscape Medical News any initiative that can expand lung cancer screening is welcome, particularly when a program may be self-sustaining.
“The interesting part of this article included the downstream revenue to help make something like this viable,” Rizzo said. “Just doing the scans is probably not going to cover the cost of the mobile unit itself, but if you take into account that other things are being found in addition to lung cancer, such as coronary abnormalities, then it becomes more cost-effective, especially if those patients are then treated at the site where the mobile unit is coming from,” he said.
Starting at square one
The first mobile CT scanner was launched in Nagano Prefecture, a rural area in Japan, in 1996. Since then, mobile screening units, primarily mounted on tractor trailers, have brought screening to centralized areas, such as shopping mall parking lots. The Levine Cancer Institute in Charlotte, North Carolina, also has a mobile CT-screening unit mounted in a modified box truck.
For Headrick and colleagues the goal was not to reinvent the wheel, but to see if a mobile lung cancer screening program could improve access and also pay for itself in a time of parsimonious support for preventive medicine.
Their first challenge was the mobile unit itself.
“CT scanners are sensitive, complex electrical machines that require climate control and a level environment to operate. Historically, they have been placed in tractor trailers and parked on level concrete slabs connected to external power supplies. We needed mobility, self-leveling, independent power, climate control, patient comfort, and drivability,” they wrote.
They assembled a team of engineers from CT and vehicle makers, and input was also provided by a thoracic surgeon, pulmonologist, radiologist, CT technician, and driver with a commercial driver’s license. Together, they designed and built the bus over 8 months. Funds for the total cost of the prototype vehicle ($650,000) came from two local nonprofit foundations. The estimated cost for a commercial version of the same vehicle was $850,000.
The Breathe Easy pilot began operation in early 2018, with the initial plan to drive the bus within a 2-hour radius of CHI Memorial Hospital, Chattanooga, Tennessee, to avoid overnight trips. The radius was later shortened to 1.5 hours when operators realized it was a burden for patients with significant screening findings to travel to as much as 4 hours (round trip) to Chattanooga for further testing.
Each screening visit takes about 15 minutes.
Cancer and other significant findings
As noted before, the bus traveled to 104 sites over 10 months, and 548 patients with a mean age of 62 were screened. Five lung cancers were identified, including two stage 1A, one stage 1A2, one stage 1B, and one stage 3A.
Two patients with early stage disease underwent stereotactic body radiation therapy, and two underwent minimally invasive surgery (a segmentectomy and a lobectomy). The patient with stage 3A disease underwent curative chemotherapy and radiation therapy. One patient with a type B1 thymoma underwent robotic-assisted thoracoscopic resection with en bloc pericardial resection and reconstruction.
A total of 51 patients had a significant pulmonary finding of Lung CT Screening Reporting and Data System (Lung-RADS) 3 or 4 and were advised to follow up with further testing, but 17 patients in this group did not pursue further testing. Of these 17 patients, 15 had been screened in a health clinic for the homeless at a rural site.
Significant nonpulmonary findings included moderate to severe coronary artery disease in 101 patients, abdominal findings in 15, thyroid abnormalities in 14, other thoracic findings in 10, and ascending aortic dilatation in 9. Of the 152 patients with nonpulmonary findings, only 13 required further testing and none required treatment.
Revisions, improvements, and priorities
The Breathe Easy bus has been in operation for more than 2 years, performing an average of approximately 100 screenings per month, with a goal of 200. The bus continued to operate throughout the COVID-19 pandemic because many patients viewed it as a safer alternative to a hospital visit, Headrick said.
Design changes planned to improve performance of the bus include a stronger chassis and structural components, as well as swapping out the 16-slice CT unit for a specially designed 64-slice mobile unit that can be operated with an iPad and provide gated coronary calcium scores.
When challenged about whether the cost of lung cancer screening is the best use of limited resources, Headrick said, “if it’s not, then when we need to go back to the drawing board and jump-start lung cancer screening.”
“When I spent a year in 2014-2015 trying to talk to radio stations, news stations, media, nobody really cared about lung cancer screening,” he said. “But as soon as I had this shiny object, which is the bus, which we labeled as the easiest and most valuable doctor visit, people had an interest.”
The pilot study was supported by local nonprofit foundations through the CHI Memorial Foundation.
This article first appeared on Medscape.com.
Results from a pilot study, published online July 13 in The Annals of Thoracic Surgery, show that the scheme is both practical and financially sustainable.
During a 10-month test run, the mobile unit screened 548 individuals at 104 sites. Five lung cancers (four of which were early stage) and a type B thymoma were discovered, and all of these individuals went on to have treatment.
Significant pulmonary findings were also discovered in 52 individuals, who were advised to undergo further testing, as well as significant nonpulmonary findings in 152 individuals (of whom 13 required further testing, but none went on to have treatment). These findings included severe coronary disease and thyroid abnormalities.
The bus reached the estimated financial break-even point of 428 scans, but future economic viability of such a program will likely rely on additional revenue from the treatment of patients with incidental findings from low-dose CT screens, acknowledged the authors, led by James R. Headrick Jr, MD, MBA, from the University of Tennessee College of Medicine in Chattanooga.
The real value of the Breathe Easy program, however, comes from bringing both patient education and lung cancer screening services to a high-risk population who might otherwise be overlooked, Headrick said in an interview with Medscape Medical News.
“We were all excited when lung screening was approved, and we got the recommendation from the United States Preventive Services Task Force [USPSTF], and the Centers for Medicare & Medicaid Services signed off on it, and we sat in our offices and clinics and hospitals — and nobody showed up. We were thinking, ‘Wow, we have this simple test, the easiest screening tool in the world, and nobody’s coming,’ “ he said.
“There was certainly an educational issue that needed to be solved,” he continued, “but we were also dealing with a population that had been told that if they smoked and didn’t live life well, there was a 100% chance they were going to get lung cancer and die,” he said.
The individuals screened in the program were very heavy smokers.
The mean pack-years of smoking was 41 — 11 pack-years higher than the minimum recommended under current lung cancer screening guidelines, and 21 pack-years higher than that recently recommended under proposed low-dose CT screening guidelines by the USPSTF.
Albert Rizzo, MD, chief medical officer for the American Lung Association, who was not involved in the study, told Medscape Medical News any initiative that can expand lung cancer screening is welcome, particularly when a program may be self-sustaining.
“The interesting part of this article included the downstream revenue to help make something like this viable,” Rizzo said. “Just doing the scans is probably not going to cover the cost of the mobile unit itself, but if you take into account that other things are being found in addition to lung cancer, such as coronary abnormalities, then it becomes more cost-effective, especially if those patients are then treated at the site where the mobile unit is coming from,” he said.
Starting at square one
The first mobile CT scanner was launched in Nagano Prefecture, a rural area in Japan, in 1996. Since then, mobile screening units, primarily mounted on tractor trailers, have brought screening to centralized areas, such as shopping mall parking lots. The Levine Cancer Institute in Charlotte, North Carolina, also has a mobile CT-screening unit mounted in a modified box truck.
For Headrick and colleagues the goal was not to reinvent the wheel, but to see if a mobile lung cancer screening program could improve access and also pay for itself in a time of parsimonious support for preventive medicine.
Their first challenge was the mobile unit itself.
“CT scanners are sensitive, complex electrical machines that require climate control and a level environment to operate. Historically, they have been placed in tractor trailers and parked on level concrete slabs connected to external power supplies. We needed mobility, self-leveling, independent power, climate control, patient comfort, and drivability,” they wrote.
They assembled a team of engineers from CT and vehicle makers, and input was also provided by a thoracic surgeon, pulmonologist, radiologist, CT technician, and driver with a commercial driver’s license. Together, they designed and built the bus over 8 months. Funds for the total cost of the prototype vehicle ($650,000) came from two local nonprofit foundations. The estimated cost for a commercial version of the same vehicle was $850,000.
The Breathe Easy pilot began operation in early 2018, with the initial plan to drive the bus within a 2-hour radius of CHI Memorial Hospital, Chattanooga, Tennessee, to avoid overnight trips. The radius was later shortened to 1.5 hours when operators realized it was a burden for patients with significant screening findings to travel to as much as 4 hours (round trip) to Chattanooga for further testing.
Each screening visit takes about 15 minutes.
Cancer and other significant findings
As noted before, the bus traveled to 104 sites over 10 months, and 548 patients with a mean age of 62 were screened. Five lung cancers were identified, including two stage 1A, one stage 1A2, one stage 1B, and one stage 3A.
Two patients with early stage disease underwent stereotactic body radiation therapy, and two underwent minimally invasive surgery (a segmentectomy and a lobectomy). The patient with stage 3A disease underwent curative chemotherapy and radiation therapy. One patient with a type B1 thymoma underwent robotic-assisted thoracoscopic resection with en bloc pericardial resection and reconstruction.
A total of 51 patients had a significant pulmonary finding of Lung CT Screening Reporting and Data System (Lung-RADS) 3 or 4 and were advised to follow up with further testing, but 17 patients in this group did not pursue further testing. Of these 17 patients, 15 had been screened in a health clinic for the homeless at a rural site.
Significant nonpulmonary findings included moderate to severe coronary artery disease in 101 patients, abdominal findings in 15, thyroid abnormalities in 14, other thoracic findings in 10, and ascending aortic dilatation in 9. Of the 152 patients with nonpulmonary findings, only 13 required further testing and none required treatment.
Revisions, improvements, and priorities
The Breathe Easy bus has been in operation for more than 2 years, performing an average of approximately 100 screenings per month, with a goal of 200. The bus continued to operate throughout the COVID-19 pandemic because many patients viewed it as a safer alternative to a hospital visit, Headrick said.
Design changes planned to improve performance of the bus include a stronger chassis and structural components, as well as swapping out the 16-slice CT unit for a specially designed 64-slice mobile unit that can be operated with an iPad and provide gated coronary calcium scores.
When challenged about whether the cost of lung cancer screening is the best use of limited resources, Headrick said, “if it’s not, then when we need to go back to the drawing board and jump-start lung cancer screening.”
“When I spent a year in 2014-2015 trying to talk to radio stations, news stations, media, nobody really cared about lung cancer screening,” he said. “But as soon as I had this shiny object, which is the bus, which we labeled as the easiest and most valuable doctor visit, people had an interest.”
The pilot study was supported by local nonprofit foundations through the CHI Memorial Foundation.
This article first appeared on Medscape.com.
ctDNA clearance tracks with PFS in NSCLC subtype
The median PFS was 9.1 months for patients with ctDNA clearance and 3.9 months for those without ctDNA clearance three to four cycles after starting treatment with osimertinib, an EGFR tyrosine kinase inhibitor (TKI), and savolitinib, a MET TKI (P = 0.0146).
“[O]ur findings indicate that EGFR-mutant ctDNA clearance may be predictive of longer PFS for patients with EGFR-mutant, MET-amplified non–small cell lung cancer and detectable ctDNA at baseline,” said investigator Ryan Hartmaier, PhD, of AstraZeneca in Boston, Mass.
Dr. Hartmaier presented these findings at the AACR virtual meeting II.
Prior results of TATTON
Interim results of the TATTON study were published earlier this year (Lancet Oncol. 2020 Mar;21[3]:373-386). The trial enrolled patients with locally advanced or metastatic EGFR-mutant, MET-amplified NSCLC who had progressed on a prior EGFR TKI. Results included patients enrolled in parts B and D.
Part B consisted of patients who had previously received a third-generation EGFR TKI and patients who had not received a third-generation EGFR TKI and were either Thr790Met negative or Thr790Met positive. There were 144 patients in part B. All received oral osimertinib at 80 mg, 138 received savolitinib at 600 mg, and 8 received savolitinib at 300 mg daily. Part D included 42 patients who had not received a third-generation EGFR TKI and were Thr790Met negative. In this cohort, patients received osimertinib at 80 mg and savolitinib at 300 mg daily.
The objective response rate (all partial responses) was 48% in part B and 64% in part D. The median PFS was 7.6 months and 9.1 months, respectively.
Alexander E. Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York said results of the TATTON study demonstrate that MET dependence is an actionable EGFR TKI resistance mechanism in EGFR-mutant lung cancers.
“We all would welcome the approval of an EGFR and MET TKI combination in the future,” Dr. Drilon said in a discussion of the study at the AACR meeting.
According to Dr. Hartmaier, MET-based resistance mechanisms are seen in up to 10% of patients with EGFR-mutated NSCLC following progression on first- and second-generation EGFR TKIs, and up to 25% of those progressing on osimertinib, a third-generation EGFR TKI.
“Nonclinical and clinical evidence suggests that combined treatment of a MET inhibitor and an EGFR TKI could overcome acquired MET-mediated resistance,” he said.
ctDNA analysis
Patients in the TATTON study had ctDNA samples collected at various time points from baseline through cycle five of treatment and until disease progression or treatment discontinuation.
Dr. Hartmaier’s analysis focused on ctDNA changes from baseline to day 1 of the third or fourth treatment cycle, time points at which the bulk of ctDNA could be observed, he said.
Among 34 evaluable patients in part B who received savolitinib at 600 mg, 22 had ctDNA clearance, and 12 had not. Among 16 evaluable patients in part D who received savolitinib at 300 mg, 13 had ctDNA clearance, and 3 had not.
Rates of ctDNA clearance were “remarkably similar” among the dosing groups, Dr. Hartmaier said.
In part B, the median PFS was 9.1 months for patients with ctDNA clearance and 3.9 months for patients without clearance (hazard ratio, 0.34; 95% confidence interval, 0.14-0.81; P = 0.0146).
Dr. Hartmaier did not present PFS results according to ctDNA clearance for patients in part D.
Dr. Drilon said serial ctDNA analyses can provide information on mechanisms of primary or acquired resistance, intra- and inter-tumoral heterogeneity, and the potential durability of benefit that can be achieved with combination targeted therapy. He acknowledged, however, that more work needs to be done in the field of MET-targeted therapy development.
“We need to work on standardizing diagnostic definitions of MET dependence, recognizing that loose definitions and poly-assay use make data challenging to interpret,” he said.
The TATTON study was supported by AstraZeneca. Dr. Hartmaier is an AstraZeneca employee and shareholder. Dr. Drilon disclosed relationships with AstraZeneca, Pfizer, Helsinn, Beigene, and other companies.
SOURCE: Hartmaier R, et al. AACR 2020, Abstract CT303.
The median PFS was 9.1 months for patients with ctDNA clearance and 3.9 months for those without ctDNA clearance three to four cycles after starting treatment with osimertinib, an EGFR tyrosine kinase inhibitor (TKI), and savolitinib, a MET TKI (P = 0.0146).
“[O]ur findings indicate that EGFR-mutant ctDNA clearance may be predictive of longer PFS for patients with EGFR-mutant, MET-amplified non–small cell lung cancer and detectable ctDNA at baseline,” said investigator Ryan Hartmaier, PhD, of AstraZeneca in Boston, Mass.
Dr. Hartmaier presented these findings at the AACR virtual meeting II.
Prior results of TATTON
Interim results of the TATTON study were published earlier this year (Lancet Oncol. 2020 Mar;21[3]:373-386). The trial enrolled patients with locally advanced or metastatic EGFR-mutant, MET-amplified NSCLC who had progressed on a prior EGFR TKI. Results included patients enrolled in parts B and D.
Part B consisted of patients who had previously received a third-generation EGFR TKI and patients who had not received a third-generation EGFR TKI and were either Thr790Met negative or Thr790Met positive. There were 144 patients in part B. All received oral osimertinib at 80 mg, 138 received savolitinib at 600 mg, and 8 received savolitinib at 300 mg daily. Part D included 42 patients who had not received a third-generation EGFR TKI and were Thr790Met negative. In this cohort, patients received osimertinib at 80 mg and savolitinib at 300 mg daily.
The objective response rate (all partial responses) was 48% in part B and 64% in part D. The median PFS was 7.6 months and 9.1 months, respectively.
Alexander E. Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York said results of the TATTON study demonstrate that MET dependence is an actionable EGFR TKI resistance mechanism in EGFR-mutant lung cancers.
“We all would welcome the approval of an EGFR and MET TKI combination in the future,” Dr. Drilon said in a discussion of the study at the AACR meeting.
According to Dr. Hartmaier, MET-based resistance mechanisms are seen in up to 10% of patients with EGFR-mutated NSCLC following progression on first- and second-generation EGFR TKIs, and up to 25% of those progressing on osimertinib, a third-generation EGFR TKI.
“Nonclinical and clinical evidence suggests that combined treatment of a MET inhibitor and an EGFR TKI could overcome acquired MET-mediated resistance,” he said.
ctDNA analysis
Patients in the TATTON study had ctDNA samples collected at various time points from baseline through cycle five of treatment and until disease progression or treatment discontinuation.
Dr. Hartmaier’s analysis focused on ctDNA changes from baseline to day 1 of the third or fourth treatment cycle, time points at which the bulk of ctDNA could be observed, he said.
Among 34 evaluable patients in part B who received savolitinib at 600 mg, 22 had ctDNA clearance, and 12 had not. Among 16 evaluable patients in part D who received savolitinib at 300 mg, 13 had ctDNA clearance, and 3 had not.
Rates of ctDNA clearance were “remarkably similar” among the dosing groups, Dr. Hartmaier said.
In part B, the median PFS was 9.1 months for patients with ctDNA clearance and 3.9 months for patients without clearance (hazard ratio, 0.34; 95% confidence interval, 0.14-0.81; P = 0.0146).
Dr. Hartmaier did not present PFS results according to ctDNA clearance for patients in part D.
Dr. Drilon said serial ctDNA analyses can provide information on mechanisms of primary or acquired resistance, intra- and inter-tumoral heterogeneity, and the potential durability of benefit that can be achieved with combination targeted therapy. He acknowledged, however, that more work needs to be done in the field of MET-targeted therapy development.
“We need to work on standardizing diagnostic definitions of MET dependence, recognizing that loose definitions and poly-assay use make data challenging to interpret,” he said.
The TATTON study was supported by AstraZeneca. Dr. Hartmaier is an AstraZeneca employee and shareholder. Dr. Drilon disclosed relationships with AstraZeneca, Pfizer, Helsinn, Beigene, and other companies.
SOURCE: Hartmaier R, et al. AACR 2020, Abstract CT303.
The median PFS was 9.1 months for patients with ctDNA clearance and 3.9 months for those without ctDNA clearance three to four cycles after starting treatment with osimertinib, an EGFR tyrosine kinase inhibitor (TKI), and savolitinib, a MET TKI (P = 0.0146).
“[O]ur findings indicate that EGFR-mutant ctDNA clearance may be predictive of longer PFS for patients with EGFR-mutant, MET-amplified non–small cell lung cancer and detectable ctDNA at baseline,” said investigator Ryan Hartmaier, PhD, of AstraZeneca in Boston, Mass.
Dr. Hartmaier presented these findings at the AACR virtual meeting II.
Prior results of TATTON
Interim results of the TATTON study were published earlier this year (Lancet Oncol. 2020 Mar;21[3]:373-386). The trial enrolled patients with locally advanced or metastatic EGFR-mutant, MET-amplified NSCLC who had progressed on a prior EGFR TKI. Results included patients enrolled in parts B and D.
Part B consisted of patients who had previously received a third-generation EGFR TKI and patients who had not received a third-generation EGFR TKI and were either Thr790Met negative or Thr790Met positive. There were 144 patients in part B. All received oral osimertinib at 80 mg, 138 received savolitinib at 600 mg, and 8 received savolitinib at 300 mg daily. Part D included 42 patients who had not received a third-generation EGFR TKI and were Thr790Met negative. In this cohort, patients received osimertinib at 80 mg and savolitinib at 300 mg daily.
The objective response rate (all partial responses) was 48% in part B and 64% in part D. The median PFS was 7.6 months and 9.1 months, respectively.
Alexander E. Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York said results of the TATTON study demonstrate that MET dependence is an actionable EGFR TKI resistance mechanism in EGFR-mutant lung cancers.
“We all would welcome the approval of an EGFR and MET TKI combination in the future,” Dr. Drilon said in a discussion of the study at the AACR meeting.
According to Dr. Hartmaier, MET-based resistance mechanisms are seen in up to 10% of patients with EGFR-mutated NSCLC following progression on first- and second-generation EGFR TKIs, and up to 25% of those progressing on osimertinib, a third-generation EGFR TKI.
“Nonclinical and clinical evidence suggests that combined treatment of a MET inhibitor and an EGFR TKI could overcome acquired MET-mediated resistance,” he said.
ctDNA analysis
Patients in the TATTON study had ctDNA samples collected at various time points from baseline through cycle five of treatment and until disease progression or treatment discontinuation.
Dr. Hartmaier’s analysis focused on ctDNA changes from baseline to day 1 of the third or fourth treatment cycle, time points at which the bulk of ctDNA could be observed, he said.
Among 34 evaluable patients in part B who received savolitinib at 600 mg, 22 had ctDNA clearance, and 12 had not. Among 16 evaluable patients in part D who received savolitinib at 300 mg, 13 had ctDNA clearance, and 3 had not.
Rates of ctDNA clearance were “remarkably similar” among the dosing groups, Dr. Hartmaier said.
In part B, the median PFS was 9.1 months for patients with ctDNA clearance and 3.9 months for patients without clearance (hazard ratio, 0.34; 95% confidence interval, 0.14-0.81; P = 0.0146).
Dr. Hartmaier did not present PFS results according to ctDNA clearance for patients in part D.
Dr. Drilon said serial ctDNA analyses can provide information on mechanisms of primary or acquired resistance, intra- and inter-tumoral heterogeneity, and the potential durability of benefit that can be achieved with combination targeted therapy. He acknowledged, however, that more work needs to be done in the field of MET-targeted therapy development.
“We need to work on standardizing diagnostic definitions of MET dependence, recognizing that loose definitions and poly-assay use make data challenging to interpret,” he said.
The TATTON study was supported by AstraZeneca. Dr. Hartmaier is an AstraZeneca employee and shareholder. Dr. Drilon disclosed relationships with AstraZeneca, Pfizer, Helsinn, Beigene, and other companies.
SOURCE: Hartmaier R, et al. AACR 2020, Abstract CT303.
FROM AACR 2020
USPSTF: Earlier lung cancer screening can double eligibility
The new proposals include lowering the age at which screening starts from 55 to 50 years, and to reduce the smoking history from 30 to 20 pack-years.
The draft recommendation from the United States Preventive Service Task Force (USPSTF) is available for public comment until August 3.
The task force recommends that adults age 50 to 80 who have a 20 pack-year or greater smoking history and currently smoke or have quit within the last 15 years undergo annual screening for lung cancer with low-dose CT,
“In my opinion, the proposed criteria by USPSTF represent a huge step in the right direction,” Lecia Sequist, MD, director of innovation at the Mass General Cancer Center in Boston, told Medscape Medical News.
“If these are adopted and implemented, we could see the benefit of screening (measured as reduction in lung cancer mortality) go from 9.8% with current parameters up to 13% with the broader parameters,” she said. “In addition, the new criteria should reduce racial disparities in screening eligibility.”
The recommendation also earned high marks from the American Lung Association.
The USPSTF has continued its ‘B’ recommendation – allowing for coverage of the screening with no cost for many under the Affordable Care Act – and is now proposing to expand the eligibility criteria “so that even more Americans at higher risk for lung cancer can be screened,” the ALA commented.
Start screening at 50
Lowering the minimum age of screening to 50 would likely mean that more Black individuals and women would be eligible for screening, the recommendation authors contend. The current screening age of 55 is currently recommended under guidelines issued by the American Association for Thoracic Surgery, American Cancer Society, American College of Chest Physicians, and National Comprehensive Cancer Network.
“African Americans have a higher risk of lung cancer, compared with whites, and this risk difference is more apparent at lower levels of smoking intensity,” they write.
As previously reported by Medscape Medical News, lung cancer screening in an urban, largely black cohort yielded roughly double the rates of positive screens and detected lung cancers compared with results from the National Lung Screening Trial, which enrolled mostly White individuals.
In addition, although lung cancer risk is greater for men than women who smoke, and women generally accumulate fewer pack-years than men, there is evidence to suggest that women who smoke may develop lung cancer earlier and with lower levels of exposure.
Therefore, “a strategy of screening persons ages 50 to 80 years who have at least a 20 pack-year smoking history and currently smoke or have quit within the past 15 years (A-50-80-20-15) would lead to a relative increase in the percentage of persons eligible for screening by 81% in men and by 96% in women,” the proposed recommendation states.
What’s the harm?
One of the major concerns about low-dose CT screening for lung cancer is the relatively high rate of false-positive results reported in two large scale clinical trials, the recommendation authors acknowledged.
For example, in the NLST, which was the basis for an earlier USPSTF recommendation (for annual screening of adults 55 to 80 years of age who have a 30 pack-year smoking history and currently smoke or have quit in the previous 15 years), the false-positive rates were 26.3% at baseline, 27.2% at year 1, and 15.9% at year 2.
Similarly, in the NELSON trial, results of which were published earlier this year, false-positive rates for men were 19.8% at baseline, 7.1% at year 1, 9% at year 3, and 3.9% at year 5.5 of screening, they noted.
“Yes, false-positive results are one of the things we need to think carefully about when embarking on lung screening,” Dr. Sequist told Medscape Medical News. “The potential harm of a false-positive (unnecessary scans, biopsies or even surgery) can be minimized by having a multidisciplinary team with experience working up lung nodules see patients who have a positive screening test. In fact, the American College of Radiology recommends that all lung screening programs be paired with such a team.”
Mass General has a pulmonary nodule clinic to evaluate screen-detected lung nodules, with the goal of minimizing unnecessary procedures, she noted.
Asked about the potential harm from radiation exposure, Sequist said that exposure from low-dose CT screening is fairly minimal, comparable to that from solar radiation at sea level over a 6-month period, or about the level from three cross-country airplane trips.
“While it is not zero radiation, there is very little concern that this low level of radiation would cause a cancer or damage one’s lungs,” she said.
Albert Rizzo, MD, chief medical officer of the ALA, said that the potential harms of unnecessary interventions are outweighed by the benefits of detecting lung cancer at an early stage.
“I think what has been learned over the last 5 years is that the original recommendations that were put out really allowed the overall rate of positivity well within what’s seen with mammography, for example, and the number of patients who have needlessly gone on to procedures remains very low, and the morbidity of those procedures remains low as well,” Dr. Rizzo told Medscape Medical News.
Not enough takers
Despite the clear benefits of low-dose CT screening, however, US screening rates for high-risk individuals are still very low, ranging from 12.3% in Massachusetts to a low of 0.5% in Nevada, according to a 2019 research report on the state of lung cancer from the ALA.
“For screening to be most effective, more of the high-risk population should be screened. Currently, screening rates are very low among those at high risk. This may be because of a lack of access or low awareness and knowledge among patients and providers. As rates vary tremendously between states, it is clear that more can be done to increase screening rates,” the report stated.
“I think that there are some mixed messages sent out into the population as to whether or not an individual patient should be screened,” Dr. Rizzo said.
He noted that some physicians may be reluctant to take on the nuanced risk–benefit discussion required, or may not have the time during a brief patient visit.
“It really boils down to that discussion between the physician and the patient who falls under these risk categories, to say, ‘Look, this is what these studies have found, and you fall under a category where if we find a cancer early, it’s very likely you’re going to be saved,’ as compared for waiting for it to present by itself,” he said.
Dr. Sequist and Dr. Rizzo have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The new proposals include lowering the age at which screening starts from 55 to 50 years, and to reduce the smoking history from 30 to 20 pack-years.
The draft recommendation from the United States Preventive Service Task Force (USPSTF) is available for public comment until August 3.
The task force recommends that adults age 50 to 80 who have a 20 pack-year or greater smoking history and currently smoke or have quit within the last 15 years undergo annual screening for lung cancer with low-dose CT,
“In my opinion, the proposed criteria by USPSTF represent a huge step in the right direction,” Lecia Sequist, MD, director of innovation at the Mass General Cancer Center in Boston, told Medscape Medical News.
“If these are adopted and implemented, we could see the benefit of screening (measured as reduction in lung cancer mortality) go from 9.8% with current parameters up to 13% with the broader parameters,” she said. “In addition, the new criteria should reduce racial disparities in screening eligibility.”
The recommendation also earned high marks from the American Lung Association.
The USPSTF has continued its ‘B’ recommendation – allowing for coverage of the screening with no cost for many under the Affordable Care Act – and is now proposing to expand the eligibility criteria “so that even more Americans at higher risk for lung cancer can be screened,” the ALA commented.
Start screening at 50
Lowering the minimum age of screening to 50 would likely mean that more Black individuals and women would be eligible for screening, the recommendation authors contend. The current screening age of 55 is currently recommended under guidelines issued by the American Association for Thoracic Surgery, American Cancer Society, American College of Chest Physicians, and National Comprehensive Cancer Network.
“African Americans have a higher risk of lung cancer, compared with whites, and this risk difference is more apparent at lower levels of smoking intensity,” they write.
As previously reported by Medscape Medical News, lung cancer screening in an urban, largely black cohort yielded roughly double the rates of positive screens and detected lung cancers compared with results from the National Lung Screening Trial, which enrolled mostly White individuals.
In addition, although lung cancer risk is greater for men than women who smoke, and women generally accumulate fewer pack-years than men, there is evidence to suggest that women who smoke may develop lung cancer earlier and with lower levels of exposure.
Therefore, “a strategy of screening persons ages 50 to 80 years who have at least a 20 pack-year smoking history and currently smoke or have quit within the past 15 years (A-50-80-20-15) would lead to a relative increase in the percentage of persons eligible for screening by 81% in men and by 96% in women,” the proposed recommendation states.
What’s the harm?
One of the major concerns about low-dose CT screening for lung cancer is the relatively high rate of false-positive results reported in two large scale clinical trials, the recommendation authors acknowledged.
For example, in the NLST, which was the basis for an earlier USPSTF recommendation (for annual screening of adults 55 to 80 years of age who have a 30 pack-year smoking history and currently smoke or have quit in the previous 15 years), the false-positive rates were 26.3% at baseline, 27.2% at year 1, and 15.9% at year 2.
Similarly, in the NELSON trial, results of which were published earlier this year, false-positive rates for men were 19.8% at baseline, 7.1% at year 1, 9% at year 3, and 3.9% at year 5.5 of screening, they noted.
“Yes, false-positive results are one of the things we need to think carefully about when embarking on lung screening,” Dr. Sequist told Medscape Medical News. “The potential harm of a false-positive (unnecessary scans, biopsies or even surgery) can be minimized by having a multidisciplinary team with experience working up lung nodules see patients who have a positive screening test. In fact, the American College of Radiology recommends that all lung screening programs be paired with such a team.”
Mass General has a pulmonary nodule clinic to evaluate screen-detected lung nodules, with the goal of minimizing unnecessary procedures, she noted.
Asked about the potential harm from radiation exposure, Sequist said that exposure from low-dose CT screening is fairly minimal, comparable to that from solar radiation at sea level over a 6-month period, or about the level from three cross-country airplane trips.
“While it is not zero radiation, there is very little concern that this low level of radiation would cause a cancer or damage one’s lungs,” she said.
Albert Rizzo, MD, chief medical officer of the ALA, said that the potential harms of unnecessary interventions are outweighed by the benefits of detecting lung cancer at an early stage.
“I think what has been learned over the last 5 years is that the original recommendations that were put out really allowed the overall rate of positivity well within what’s seen with mammography, for example, and the number of patients who have needlessly gone on to procedures remains very low, and the morbidity of those procedures remains low as well,” Dr. Rizzo told Medscape Medical News.
Not enough takers
Despite the clear benefits of low-dose CT screening, however, US screening rates for high-risk individuals are still very low, ranging from 12.3% in Massachusetts to a low of 0.5% in Nevada, according to a 2019 research report on the state of lung cancer from the ALA.
“For screening to be most effective, more of the high-risk population should be screened. Currently, screening rates are very low among those at high risk. This may be because of a lack of access or low awareness and knowledge among patients and providers. As rates vary tremendously between states, it is clear that more can be done to increase screening rates,” the report stated.
“I think that there are some mixed messages sent out into the population as to whether or not an individual patient should be screened,” Dr. Rizzo said.
He noted that some physicians may be reluctant to take on the nuanced risk–benefit discussion required, or may not have the time during a brief patient visit.
“It really boils down to that discussion between the physician and the patient who falls under these risk categories, to say, ‘Look, this is what these studies have found, and you fall under a category where if we find a cancer early, it’s very likely you’re going to be saved,’ as compared for waiting for it to present by itself,” he said.
Dr. Sequist and Dr. Rizzo have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The new proposals include lowering the age at which screening starts from 55 to 50 years, and to reduce the smoking history from 30 to 20 pack-years.
The draft recommendation from the United States Preventive Service Task Force (USPSTF) is available for public comment until August 3.
The task force recommends that adults age 50 to 80 who have a 20 pack-year or greater smoking history and currently smoke or have quit within the last 15 years undergo annual screening for lung cancer with low-dose CT,
“In my opinion, the proposed criteria by USPSTF represent a huge step in the right direction,” Lecia Sequist, MD, director of innovation at the Mass General Cancer Center in Boston, told Medscape Medical News.
“If these are adopted and implemented, we could see the benefit of screening (measured as reduction in lung cancer mortality) go from 9.8% with current parameters up to 13% with the broader parameters,” she said. “In addition, the new criteria should reduce racial disparities in screening eligibility.”
The recommendation also earned high marks from the American Lung Association.
The USPSTF has continued its ‘B’ recommendation – allowing for coverage of the screening with no cost for many under the Affordable Care Act – and is now proposing to expand the eligibility criteria “so that even more Americans at higher risk for lung cancer can be screened,” the ALA commented.
Start screening at 50
Lowering the minimum age of screening to 50 would likely mean that more Black individuals and women would be eligible for screening, the recommendation authors contend. The current screening age of 55 is currently recommended under guidelines issued by the American Association for Thoracic Surgery, American Cancer Society, American College of Chest Physicians, and National Comprehensive Cancer Network.
“African Americans have a higher risk of lung cancer, compared with whites, and this risk difference is more apparent at lower levels of smoking intensity,” they write.
As previously reported by Medscape Medical News, lung cancer screening in an urban, largely black cohort yielded roughly double the rates of positive screens and detected lung cancers compared with results from the National Lung Screening Trial, which enrolled mostly White individuals.
In addition, although lung cancer risk is greater for men than women who smoke, and women generally accumulate fewer pack-years than men, there is evidence to suggest that women who smoke may develop lung cancer earlier and with lower levels of exposure.
Therefore, “a strategy of screening persons ages 50 to 80 years who have at least a 20 pack-year smoking history and currently smoke or have quit within the past 15 years (A-50-80-20-15) would lead to a relative increase in the percentage of persons eligible for screening by 81% in men and by 96% in women,” the proposed recommendation states.
What’s the harm?
One of the major concerns about low-dose CT screening for lung cancer is the relatively high rate of false-positive results reported in two large scale clinical trials, the recommendation authors acknowledged.
For example, in the NLST, which was the basis for an earlier USPSTF recommendation (for annual screening of adults 55 to 80 years of age who have a 30 pack-year smoking history and currently smoke or have quit in the previous 15 years), the false-positive rates were 26.3% at baseline, 27.2% at year 1, and 15.9% at year 2.
Similarly, in the NELSON trial, results of which were published earlier this year, false-positive rates for men were 19.8% at baseline, 7.1% at year 1, 9% at year 3, and 3.9% at year 5.5 of screening, they noted.
“Yes, false-positive results are one of the things we need to think carefully about when embarking on lung screening,” Dr. Sequist told Medscape Medical News. “The potential harm of a false-positive (unnecessary scans, biopsies or even surgery) can be minimized by having a multidisciplinary team with experience working up lung nodules see patients who have a positive screening test. In fact, the American College of Radiology recommends that all lung screening programs be paired with such a team.”
Mass General has a pulmonary nodule clinic to evaluate screen-detected lung nodules, with the goal of minimizing unnecessary procedures, she noted.
Asked about the potential harm from radiation exposure, Sequist said that exposure from low-dose CT screening is fairly minimal, comparable to that from solar radiation at sea level over a 6-month period, or about the level from three cross-country airplane trips.
“While it is not zero radiation, there is very little concern that this low level of radiation would cause a cancer or damage one’s lungs,” she said.
Albert Rizzo, MD, chief medical officer of the ALA, said that the potential harms of unnecessary interventions are outweighed by the benefits of detecting lung cancer at an early stage.
“I think what has been learned over the last 5 years is that the original recommendations that were put out really allowed the overall rate of positivity well within what’s seen with mammography, for example, and the number of patients who have needlessly gone on to procedures remains very low, and the morbidity of those procedures remains low as well,” Dr. Rizzo told Medscape Medical News.
Not enough takers
Despite the clear benefits of low-dose CT screening, however, US screening rates for high-risk individuals are still very low, ranging from 12.3% in Massachusetts to a low of 0.5% in Nevada, according to a 2019 research report on the state of lung cancer from the ALA.
“For screening to be most effective, more of the high-risk population should be screened. Currently, screening rates are very low among those at high risk. This may be because of a lack of access or low awareness and knowledge among patients and providers. As rates vary tremendously between states, it is clear that more can be done to increase screening rates,” the report stated.
“I think that there are some mixed messages sent out into the population as to whether or not an individual patient should be screened,” Dr. Rizzo said.
He noted that some physicians may be reluctant to take on the nuanced risk–benefit discussion required, or may not have the time during a brief patient visit.
“It really boils down to that discussion between the physician and the patient who falls under these risk categories, to say, ‘Look, this is what these studies have found, and you fall under a category where if we find a cancer early, it’s very likely you’re going to be saved,’ as compared for waiting for it to present by itself,” he said.
Dr. Sequist and Dr. Rizzo have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Could being active reduce cancer death risk from alcohol?
Moderate drinking not a problem
concludes a new observational study involving 50,000-plus British adults.
Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.
The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”
Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.
Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.
But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).
That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.
The study was published online May 14 in the International Journal of Cancer.
The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.
Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.
Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”
However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men.
Study author Dr. Stamatakis commented on the alcohol debate.
“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”
Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”
This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.
However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.
Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”
Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.
But that risk increase is not clinically relevant, she added.
Mean 10 years of follow-up
The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).
The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.
Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.
Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.
Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.
The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.
The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.
For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.
These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.
The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.
The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.
“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write.
Dr. Stamatakis practices what he advocates, but is not a teetotaler.
“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.
Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.
This article first appeared on Medscape.com.
Moderate drinking not a problem
Moderate drinking not a problem
concludes a new observational study involving 50,000-plus British adults.
Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.
The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”
Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.
Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.
But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).
That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.
The study was published online May 14 in the International Journal of Cancer.
The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.
Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.
Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”
However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men.
Study author Dr. Stamatakis commented on the alcohol debate.
“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”
Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”
This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.
However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.
Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”
Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.
But that risk increase is not clinically relevant, she added.
Mean 10 years of follow-up
The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).
The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.
Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.
Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.
Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.
The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.
The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.
For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.
These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.
The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.
The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.
“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write.
Dr. Stamatakis practices what he advocates, but is not a teetotaler.
“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.
Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.
This article first appeared on Medscape.com.
concludes a new observational study involving 50,000-plus British adults.
Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.
The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”
Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.
Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.
But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).
That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.
The study was published online May 14 in the International Journal of Cancer.
The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.
Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.
Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”
However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men.
Study author Dr. Stamatakis commented on the alcohol debate.
“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”
Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”
This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.
However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.
Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”
Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.
But that risk increase is not clinically relevant, she added.
Mean 10 years of follow-up
The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).
The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.
Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.
Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.
Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.
The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.
The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.
For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.
These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.
The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.
The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.
“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write.
Dr. Stamatakis practices what he advocates, but is not a teetotaler.
“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.
Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.
This article first appeared on Medscape.com.
Radiomics can identify high-risk early stage lung cancer
Radiomics, a growing area of cancer research that extracts noninvasive biomarkers from medical imaging, may be able to improve lung cancer screening by identifying patients with early stage disease at high risk for poorer outcomes.
This is the conclusion from a group of researchers who used data from the National Lung Screening Trial (NLST) to develop and validate a model based on radiomics that could identify a vulnerable high-risk group of early stage patients associated with poor outcomes. These patients would generally require aggressive follow-up and/or adjuvant therapy.
The study was published June 29 in Nature Scientific Reports.
Radiomics, also known as quantitative image features, are noninvasive biomarkers that are generated from medical imaging. An emerging translational field of research, radiomics extracts large amounts of features from radiographic medical images using data-characterization algorithms, which reflect the underlying tumor pathophysiology and heterogeneity.
The authors note that radiomics has many advantages over circulating and tissue-based biomarkers, as these quantitative image features are rapidly calculated from standard-of-care imaging and reflect the entire tumor burden – and not just a sample as is the case with tissue-based biomarkers.
“We view radiomics as a decision support tool across the cancer control continuum, whether it be screening and early detection, diagnosis, prognostication, or treatment response,” said lead author Matthew B. Schabath, PhD, associate member in cancer epidemiology at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida.
“Radiomic features are generated from standard-of-care imaging and validated radiomic models can provide real-time decision support information to clinicians,” he explained.
Last year, another study showed that combining radiomics and imaging may be able to determine which patients with lung cancer were most likely to respond to chemotherapy. The researchers used CT imaging of radiomic features from within and outside the lung nodule and found it could predict time to progression and overall survival, as well as response to chemotherapy, in patients with non–small cell lung cancer (NSCLC).
Anant Madabhushi, PhD, a professor of biomedical engineering and director of the Center for Computational Imaging and Personalized Diagnostics at Case Western Reserve University, Cleveland, commented that the new study is “complementary and supports the premise that radiomics both from inside and outside the tumor can tell us about outcome and treatment response.”
Dr. Madabhushi also noted his group has released several other studies along similar lines, including a study showing how radiomics can predict the benefit of adjuvant therapy in lung cancer, a study showing how radiomics can predict recurrence in early stage NSCLC, and a study showing that radiomics can predict survival and response to immunotherapy in NSCLC.
Improving current lung cancer screening
The landmark NLST showed that, as compared with chest x-rays, low-dose helical computed tomography (LDCT) was associated with a 20% relative reduction in lung cancer mortality in high-risk individuals. However, LDCT screening can lead to overdiagnosis and subsequent overtreatment of slow-growing, indolent cancers.
“Current lung cancer screening inclusion criteria in the US are largely based on the criteria used in the NLST,” Dr. Schabath told Medscape Medical News. “Though the NLST clearly demonstrated that screening LDCT is a lifesaving tool, the NLST was not designed to create public policy.”
He pointed out that fewer than 30% of Americans diagnosed with lung cancer meet the current screening entry criteria and that subsequent trials (e.g., NELSON, LUSI, or MILD) used broader and more inclusive criteria and also showed the efficacy of LDCT for early detection of lung cancer. “Thus, there should be consideration in making the lung cancer screening guidelines more inclusive,” said Dr. Schabath.
“Additionally, adjunct risk-stratification tools, such as blood-based biomarkers, could be an important complement to determine who should be part of a lung cancer screening program,” he said. “This could be particularly salient for people who have no or very few risk factors, such as never smokers.”
Pinpointing poor outcomes
In the current study, Dr. Schabath and colleagues used publicly available data and LDCT images from the NLST to generate radiomic features from screen detected, incidentally-diagnosed lung cancers. Radiomic features describing size, shape, volume, and textural characteristics were then calculated from both the intratumoral and peritumoral regions.
Patients were divided into training and test cohorts, and an external cohort of non-screen-detected lung cancer patients was used for further validation. There were no statistically significant differences between training and test cohorts for most demographics, including age, sex, smoking status, number of pack-years smoked, treatment, stage, and baseline screening result. However, self-reported chronic obstructive pulmonary disease (COPD) was significantly higher in the test cohort compared with the training group (16% vs. 7%; P = .02).
A total of 91 stable and reproducible radiomics features (peritumoral and intratumoral) were identified and 40 (26 peritumoral and 14 intratumoral) were significantly associated with overall survival in the training cohort. The features were subsequently narrowed to four, and backward elimination analyses identified a single model. Patients were then stratified into three risk-groups: low risk, intermediate risk, and high risk.
According to their model, the high-risk group had worse overall survival (hazard ratio, 9.91; 25% 2.5-year and 0% 5-year OS) as compared with the low-risk group (HR, 1.00; 93% 2.5-year and 78% 5-year OS).
The final model was validated in the test group and then replicated in the non–screen-detected patients with adenocarcinoma patients. Since the disease stage differed significantly across the risk groups, the model was stratified by stage and the authors found “compelling” results among early-stage patients, who generally have good outcomes. In this subset, the high-risk group was associated with a worse overall survival (HR, 2.63; 56% 2.5-year and 42% 5-year OS) vs. the low-risk group (HR, 1.00; 75% 2.5-year and 75% 5-year OS).
“We have ongoing studies to determine if these results are consistent in the real-world setting of lung cancer screening across multiple centers,” said Dr. Schabath. “If the NELSON, LUSI, or MILD trial data become publicly available, we will certainly pursue validating our results in those clinical trials.”
The study was funded by the National Cancer Institute. Dr. Schabath and Dr. Madabhushi have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Radiomics, a growing area of cancer research that extracts noninvasive biomarkers from medical imaging, may be able to improve lung cancer screening by identifying patients with early stage disease at high risk for poorer outcomes.
This is the conclusion from a group of researchers who used data from the National Lung Screening Trial (NLST) to develop and validate a model based on radiomics that could identify a vulnerable high-risk group of early stage patients associated with poor outcomes. These patients would generally require aggressive follow-up and/or adjuvant therapy.
The study was published June 29 in Nature Scientific Reports.
Radiomics, also known as quantitative image features, are noninvasive biomarkers that are generated from medical imaging. An emerging translational field of research, radiomics extracts large amounts of features from radiographic medical images using data-characterization algorithms, which reflect the underlying tumor pathophysiology and heterogeneity.
The authors note that radiomics has many advantages over circulating and tissue-based biomarkers, as these quantitative image features are rapidly calculated from standard-of-care imaging and reflect the entire tumor burden – and not just a sample as is the case with tissue-based biomarkers.
“We view radiomics as a decision support tool across the cancer control continuum, whether it be screening and early detection, diagnosis, prognostication, or treatment response,” said lead author Matthew B. Schabath, PhD, associate member in cancer epidemiology at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida.
“Radiomic features are generated from standard-of-care imaging and validated radiomic models can provide real-time decision support information to clinicians,” he explained.
Last year, another study showed that combining radiomics and imaging may be able to determine which patients with lung cancer were most likely to respond to chemotherapy. The researchers used CT imaging of radiomic features from within and outside the lung nodule and found it could predict time to progression and overall survival, as well as response to chemotherapy, in patients with non–small cell lung cancer (NSCLC).
Anant Madabhushi, PhD, a professor of biomedical engineering and director of the Center for Computational Imaging and Personalized Diagnostics at Case Western Reserve University, Cleveland, commented that the new study is “complementary and supports the premise that radiomics both from inside and outside the tumor can tell us about outcome and treatment response.”
Dr. Madabhushi also noted his group has released several other studies along similar lines, including a study showing how radiomics can predict the benefit of adjuvant therapy in lung cancer, a study showing how radiomics can predict recurrence in early stage NSCLC, and a study showing that radiomics can predict survival and response to immunotherapy in NSCLC.
Improving current lung cancer screening
The landmark NLST showed that, as compared with chest x-rays, low-dose helical computed tomography (LDCT) was associated with a 20% relative reduction in lung cancer mortality in high-risk individuals. However, LDCT screening can lead to overdiagnosis and subsequent overtreatment of slow-growing, indolent cancers.
“Current lung cancer screening inclusion criteria in the US are largely based on the criteria used in the NLST,” Dr. Schabath told Medscape Medical News. “Though the NLST clearly demonstrated that screening LDCT is a lifesaving tool, the NLST was not designed to create public policy.”
He pointed out that fewer than 30% of Americans diagnosed with lung cancer meet the current screening entry criteria and that subsequent trials (e.g., NELSON, LUSI, or MILD) used broader and more inclusive criteria and also showed the efficacy of LDCT for early detection of lung cancer. “Thus, there should be consideration in making the lung cancer screening guidelines more inclusive,” said Dr. Schabath.
“Additionally, adjunct risk-stratification tools, such as blood-based biomarkers, could be an important complement to determine who should be part of a lung cancer screening program,” he said. “This could be particularly salient for people who have no or very few risk factors, such as never smokers.”
Pinpointing poor outcomes
In the current study, Dr. Schabath and colleagues used publicly available data and LDCT images from the NLST to generate radiomic features from screen detected, incidentally-diagnosed lung cancers. Radiomic features describing size, shape, volume, and textural characteristics were then calculated from both the intratumoral and peritumoral regions.
Patients were divided into training and test cohorts, and an external cohort of non-screen-detected lung cancer patients was used for further validation. There were no statistically significant differences between training and test cohorts for most demographics, including age, sex, smoking status, number of pack-years smoked, treatment, stage, and baseline screening result. However, self-reported chronic obstructive pulmonary disease (COPD) was significantly higher in the test cohort compared with the training group (16% vs. 7%; P = .02).
A total of 91 stable and reproducible radiomics features (peritumoral and intratumoral) were identified and 40 (26 peritumoral and 14 intratumoral) were significantly associated with overall survival in the training cohort. The features were subsequently narrowed to four, and backward elimination analyses identified a single model. Patients were then stratified into three risk-groups: low risk, intermediate risk, and high risk.
According to their model, the high-risk group had worse overall survival (hazard ratio, 9.91; 25% 2.5-year and 0% 5-year OS) as compared with the low-risk group (HR, 1.00; 93% 2.5-year and 78% 5-year OS).
The final model was validated in the test group and then replicated in the non–screen-detected patients with adenocarcinoma patients. Since the disease stage differed significantly across the risk groups, the model was stratified by stage and the authors found “compelling” results among early-stage patients, who generally have good outcomes. In this subset, the high-risk group was associated with a worse overall survival (HR, 2.63; 56% 2.5-year and 42% 5-year OS) vs. the low-risk group (HR, 1.00; 75% 2.5-year and 75% 5-year OS).
“We have ongoing studies to determine if these results are consistent in the real-world setting of lung cancer screening across multiple centers,” said Dr. Schabath. “If the NELSON, LUSI, or MILD trial data become publicly available, we will certainly pursue validating our results in those clinical trials.”
The study was funded by the National Cancer Institute. Dr. Schabath and Dr. Madabhushi have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Radiomics, a growing area of cancer research that extracts noninvasive biomarkers from medical imaging, may be able to improve lung cancer screening by identifying patients with early stage disease at high risk for poorer outcomes.
This is the conclusion from a group of researchers who used data from the National Lung Screening Trial (NLST) to develop and validate a model based on radiomics that could identify a vulnerable high-risk group of early stage patients associated with poor outcomes. These patients would generally require aggressive follow-up and/or adjuvant therapy.
The study was published June 29 in Nature Scientific Reports.
Radiomics, also known as quantitative image features, are noninvasive biomarkers that are generated from medical imaging. An emerging translational field of research, radiomics extracts large amounts of features from radiographic medical images using data-characterization algorithms, which reflect the underlying tumor pathophysiology and heterogeneity.
The authors note that radiomics has many advantages over circulating and tissue-based biomarkers, as these quantitative image features are rapidly calculated from standard-of-care imaging and reflect the entire tumor burden – and not just a sample as is the case with tissue-based biomarkers.
“We view radiomics as a decision support tool across the cancer control continuum, whether it be screening and early detection, diagnosis, prognostication, or treatment response,” said lead author Matthew B. Schabath, PhD, associate member in cancer epidemiology at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida.
“Radiomic features are generated from standard-of-care imaging and validated radiomic models can provide real-time decision support information to clinicians,” he explained.
Last year, another study showed that combining radiomics and imaging may be able to determine which patients with lung cancer were most likely to respond to chemotherapy. The researchers used CT imaging of radiomic features from within and outside the lung nodule and found it could predict time to progression and overall survival, as well as response to chemotherapy, in patients with non–small cell lung cancer (NSCLC).
Anant Madabhushi, PhD, a professor of biomedical engineering and director of the Center for Computational Imaging and Personalized Diagnostics at Case Western Reserve University, Cleveland, commented that the new study is “complementary and supports the premise that radiomics both from inside and outside the tumor can tell us about outcome and treatment response.”
Dr. Madabhushi also noted his group has released several other studies along similar lines, including a study showing how radiomics can predict the benefit of adjuvant therapy in lung cancer, a study showing how radiomics can predict recurrence in early stage NSCLC, and a study showing that radiomics can predict survival and response to immunotherapy in NSCLC.
Improving current lung cancer screening
The landmark NLST showed that, as compared with chest x-rays, low-dose helical computed tomography (LDCT) was associated with a 20% relative reduction in lung cancer mortality in high-risk individuals. However, LDCT screening can lead to overdiagnosis and subsequent overtreatment of slow-growing, indolent cancers.
“Current lung cancer screening inclusion criteria in the US are largely based on the criteria used in the NLST,” Dr. Schabath told Medscape Medical News. “Though the NLST clearly demonstrated that screening LDCT is a lifesaving tool, the NLST was not designed to create public policy.”
He pointed out that fewer than 30% of Americans diagnosed with lung cancer meet the current screening entry criteria and that subsequent trials (e.g., NELSON, LUSI, or MILD) used broader and more inclusive criteria and also showed the efficacy of LDCT for early detection of lung cancer. “Thus, there should be consideration in making the lung cancer screening guidelines more inclusive,” said Dr. Schabath.
“Additionally, adjunct risk-stratification tools, such as blood-based biomarkers, could be an important complement to determine who should be part of a lung cancer screening program,” he said. “This could be particularly salient for people who have no or very few risk factors, such as never smokers.”
Pinpointing poor outcomes
In the current study, Dr. Schabath and colleagues used publicly available data and LDCT images from the NLST to generate radiomic features from screen detected, incidentally-diagnosed lung cancers. Radiomic features describing size, shape, volume, and textural characteristics were then calculated from both the intratumoral and peritumoral regions.
Patients were divided into training and test cohorts, and an external cohort of non-screen-detected lung cancer patients was used for further validation. There were no statistically significant differences between training and test cohorts for most demographics, including age, sex, smoking status, number of pack-years smoked, treatment, stage, and baseline screening result. However, self-reported chronic obstructive pulmonary disease (COPD) was significantly higher in the test cohort compared with the training group (16% vs. 7%; P = .02).
A total of 91 stable and reproducible radiomics features (peritumoral and intratumoral) were identified and 40 (26 peritumoral and 14 intratumoral) were significantly associated with overall survival in the training cohort. The features were subsequently narrowed to four, and backward elimination analyses identified a single model. Patients were then stratified into three risk-groups: low risk, intermediate risk, and high risk.
According to their model, the high-risk group had worse overall survival (hazard ratio, 9.91; 25% 2.5-year and 0% 5-year OS) as compared with the low-risk group (HR, 1.00; 93% 2.5-year and 78% 5-year OS).
The final model was validated in the test group and then replicated in the non–screen-detected patients with adenocarcinoma patients. Since the disease stage differed significantly across the risk groups, the model was stratified by stage and the authors found “compelling” results among early-stage patients, who generally have good outcomes. In this subset, the high-risk group was associated with a worse overall survival (HR, 2.63; 56% 2.5-year and 42% 5-year OS) vs. the low-risk group (HR, 1.00; 75% 2.5-year and 75% 5-year OS).
“We have ongoing studies to determine if these results are consistent in the real-world setting of lung cancer screening across multiple centers,” said Dr. Schabath. “If the NELSON, LUSI, or MILD trial data become publicly available, we will certainly pursue validating our results in those clinical trials.”
The study was funded by the National Cancer Institute. Dr. Schabath and Dr. Madabhushi have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
FDA approves new indications for pembrolizumab
The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.
The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.
In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.
The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.
Accelerated approval to treat solid tumors
The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.
The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).
The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.
Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.
The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.
The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.
Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
New option for recurrent or metastatic cSCC
Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.
The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.
The objective response rate was 34%, and the median duration of response was not reached.
Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.
The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.
The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.
In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.
The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.
Accelerated approval to treat solid tumors
The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.
The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).
The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.
Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.
The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.
The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.
Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
New option for recurrent or metastatic cSCC
Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.
The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.
The objective response rate was 34%, and the median duration of response was not reached.
Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.
The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.
The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.
In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.
The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.
Accelerated approval to treat solid tumors
The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.
The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).
The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.
Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.
The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.
The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.
Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
New option for recurrent or metastatic cSCC
Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.
The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.
The objective response rate was 34%, and the median duration of response was not reached.
Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.
Tiragolumab plus atezolizumab active in PD-L1+ NSCLC
The combination of the anti-TIGIT antibody tiragolumab with the PD-L1 inhibitor atezolizumab was well tolerated and showed preliminary activity in the phase 1b portion of the study, according to investigator Johanna C. Bendell, MD, of Sarah Cannon Research Institute/Tennessee Oncology in Nashville, Tenn.
Objective responses occurred mainly in chemoimmunotherapy-naive, PD-L1-positive tumors. In an expansion cohort of 13 patients with PD-L1-positive non–small cell lung cancer (NSCLC), the confirmed overall response rate was 46%, with several responses demonstrating durability.
Dr. Bendell reported these results at the AACR virtual meeting II.
While several important research questions remain, the results in the lung cancer expansion cohort were encouraging, particularly in patients who were smokers and previous smokers, said invited discussant Michele Teng, PhD, of QIMR Berghofer Medical Research Institute in Brisbane, Australia.
“Although it was [a] small cohort, the data suggest promising duration of response in some of the patients [n = 4] who have been under study for more than 700 days,” Dr. Teng said.
Based on the preliminary safety and activity seen in this study, the combination of tiragolumab and atezolizumab is being evaluated in a randomized, placebo-controlled phase 2 study, and a phase 3 study is recruiting.
Rationale, design, and safety
TIGIT is a novel inhibitory receptor expressed on multiple immune cells, especially CD8-positive T cells and natural killer cells, Dr. Bendell explained. She added that TIGIT is coexpressed with PD-1 on immune cells.
“Using anti-TIGIT antibodies to prevent TIGIT from binding, and cotargeting TIGIT and PD-L1, may restore antitumor response and enhance anti-PD-L1 effect,” Dr. Bendell said.
The phase 1 study Dr. Bendell presented, known as GO30103, was designed to evaluate tiragolumab as a single agent and in combination with atezolizumab in advanced solid tumors.
There were 24 patients in the phase 1a portion of GO30103, which was intended to determine the preliminary safety, tolerability, and recommended phase 2 dose of tiragolumab. There were 49 patients treated with tiragolumab plus atezolizumab in the phase 1b portion, which was intended to provide data on pharmacokinetics as well as preliminary antitumor activity of the combination.
No dose-limiting toxicities were seen in either cohort. The recommended phase 2 dose of tiragolumab was 600 mg every 3 weeks.
Tiragolumab was well tolerated in the phase 1a and 1b portions of the trial, according to Dr. Bendell.
“Immune-related adverse events were seen, but their incidence was not out of proportion to events seen with atezolizumab alone,” she said.
Treatment-related grade 3-4 adverse events occurred in one patient (4%) in the phase 1a portion of the trial and two patients (4%) in the phase 1b portion. There were no grade 5 adverse events related to treatment.
Efficacy and next steps
No objective responses were seen with tiragolumab monotherapy, although several patients did exhibit tumor reduction.
“We were not really expecting much single-agent activity of the anti-TIGIT drug,” Dr. Bendell said. “There’s some preclinical data that suggests that TIGIT may be more important as a single agent in earlier stages of cancer.”
In contrast, the combination of tiragolumab and atezolizumab resulted in several responses, including one in a patient with PD-L1-positive NSCLC who was previously treated with immunotherapy, according to Dr. Bendell.
The 13-patient expansion cohort of patients with PD-L1-positive NSCLC were treated at the recommended phase 2 dose of tiragolumab and atezolizumab. In these chemoimmunotherapy-naive patients, the overall response rate was 46%. Responses occurred in 6 of 13 patients and included 2 complete responses. Four patients had stable disease, so the disease control rate was 85% (11/13).
Based on that expansion cohort, a randomized, phase 2 study called CITYSCAPE was initiated. Results of CITYSCAPE were recently presented as part of the American Society of Clinical Oncology virtual scientific program.
In that study, tiragolumab plus atezolizumab improved the overall response rate and progression-free survival when compared with placebo plus atezolizumab. More substantial improvement was seen in the subgroup of patients with PD-L1 tumor proportion scores of 50% or greater.
The activity and safety of tiragolumab plus atezolizumab will be confirmed in the ongoing SKYSCRAPER-01 trial (NCT04294810), a phase 3 study of first-line treatment in patients with NSCLC and a PD-L1 tumor proportion score of 50% or greater, according to investigators.
The phase 1 study presented by Dr. Bendell was sponsored by Genentech. Dr. Bendell disclosed relationships with Genentech/Roche, Gilead, Five Prime, Lilly, and other companies.
SOURCE: Bendell JC et al. AACR 2020, Abstract CT302.
The combination of the anti-TIGIT antibody tiragolumab with the PD-L1 inhibitor atezolizumab was well tolerated and showed preliminary activity in the phase 1b portion of the study, according to investigator Johanna C. Bendell, MD, of Sarah Cannon Research Institute/Tennessee Oncology in Nashville, Tenn.
Objective responses occurred mainly in chemoimmunotherapy-naive, PD-L1-positive tumors. In an expansion cohort of 13 patients with PD-L1-positive non–small cell lung cancer (NSCLC), the confirmed overall response rate was 46%, with several responses demonstrating durability.
Dr. Bendell reported these results at the AACR virtual meeting II.
While several important research questions remain, the results in the lung cancer expansion cohort were encouraging, particularly in patients who were smokers and previous smokers, said invited discussant Michele Teng, PhD, of QIMR Berghofer Medical Research Institute in Brisbane, Australia.
“Although it was [a] small cohort, the data suggest promising duration of response in some of the patients [n = 4] who have been under study for more than 700 days,” Dr. Teng said.
Based on the preliminary safety and activity seen in this study, the combination of tiragolumab and atezolizumab is being evaluated in a randomized, placebo-controlled phase 2 study, and a phase 3 study is recruiting.
Rationale, design, and safety
TIGIT is a novel inhibitory receptor expressed on multiple immune cells, especially CD8-positive T cells and natural killer cells, Dr. Bendell explained. She added that TIGIT is coexpressed with PD-1 on immune cells.
“Using anti-TIGIT antibodies to prevent TIGIT from binding, and cotargeting TIGIT and PD-L1, may restore antitumor response and enhance anti-PD-L1 effect,” Dr. Bendell said.
The phase 1 study Dr. Bendell presented, known as GO30103, was designed to evaluate tiragolumab as a single agent and in combination with atezolizumab in advanced solid tumors.
There were 24 patients in the phase 1a portion of GO30103, which was intended to determine the preliminary safety, tolerability, and recommended phase 2 dose of tiragolumab. There were 49 patients treated with tiragolumab plus atezolizumab in the phase 1b portion, which was intended to provide data on pharmacokinetics as well as preliminary antitumor activity of the combination.
No dose-limiting toxicities were seen in either cohort. The recommended phase 2 dose of tiragolumab was 600 mg every 3 weeks.
Tiragolumab was well tolerated in the phase 1a and 1b portions of the trial, according to Dr. Bendell.
“Immune-related adverse events were seen, but their incidence was not out of proportion to events seen with atezolizumab alone,” she said.
Treatment-related grade 3-4 adverse events occurred in one patient (4%) in the phase 1a portion of the trial and two patients (4%) in the phase 1b portion. There were no grade 5 adverse events related to treatment.
Efficacy and next steps
No objective responses were seen with tiragolumab monotherapy, although several patients did exhibit tumor reduction.
“We were not really expecting much single-agent activity of the anti-TIGIT drug,” Dr. Bendell said. “There’s some preclinical data that suggests that TIGIT may be more important as a single agent in earlier stages of cancer.”
In contrast, the combination of tiragolumab and atezolizumab resulted in several responses, including one in a patient with PD-L1-positive NSCLC who was previously treated with immunotherapy, according to Dr. Bendell.
The 13-patient expansion cohort of patients with PD-L1-positive NSCLC were treated at the recommended phase 2 dose of tiragolumab and atezolizumab. In these chemoimmunotherapy-naive patients, the overall response rate was 46%. Responses occurred in 6 of 13 patients and included 2 complete responses. Four patients had stable disease, so the disease control rate was 85% (11/13).
Based on that expansion cohort, a randomized, phase 2 study called CITYSCAPE was initiated. Results of CITYSCAPE were recently presented as part of the American Society of Clinical Oncology virtual scientific program.
In that study, tiragolumab plus atezolizumab improved the overall response rate and progression-free survival when compared with placebo plus atezolizumab. More substantial improvement was seen in the subgroup of patients with PD-L1 tumor proportion scores of 50% or greater.
The activity and safety of tiragolumab plus atezolizumab will be confirmed in the ongoing SKYSCRAPER-01 trial (NCT04294810), a phase 3 study of first-line treatment in patients with NSCLC and a PD-L1 tumor proportion score of 50% or greater, according to investigators.
The phase 1 study presented by Dr. Bendell was sponsored by Genentech. Dr. Bendell disclosed relationships with Genentech/Roche, Gilead, Five Prime, Lilly, and other companies.
SOURCE: Bendell JC et al. AACR 2020, Abstract CT302.
The combination of the anti-TIGIT antibody tiragolumab with the PD-L1 inhibitor atezolizumab was well tolerated and showed preliminary activity in the phase 1b portion of the study, according to investigator Johanna C. Bendell, MD, of Sarah Cannon Research Institute/Tennessee Oncology in Nashville, Tenn.
Objective responses occurred mainly in chemoimmunotherapy-naive, PD-L1-positive tumors. In an expansion cohort of 13 patients with PD-L1-positive non–small cell lung cancer (NSCLC), the confirmed overall response rate was 46%, with several responses demonstrating durability.
Dr. Bendell reported these results at the AACR virtual meeting II.
While several important research questions remain, the results in the lung cancer expansion cohort were encouraging, particularly in patients who were smokers and previous smokers, said invited discussant Michele Teng, PhD, of QIMR Berghofer Medical Research Institute in Brisbane, Australia.
“Although it was [a] small cohort, the data suggest promising duration of response in some of the patients [n = 4] who have been under study for more than 700 days,” Dr. Teng said.
Based on the preliminary safety and activity seen in this study, the combination of tiragolumab and atezolizumab is being evaluated in a randomized, placebo-controlled phase 2 study, and a phase 3 study is recruiting.
Rationale, design, and safety
TIGIT is a novel inhibitory receptor expressed on multiple immune cells, especially CD8-positive T cells and natural killer cells, Dr. Bendell explained. She added that TIGIT is coexpressed with PD-1 on immune cells.
“Using anti-TIGIT antibodies to prevent TIGIT from binding, and cotargeting TIGIT and PD-L1, may restore antitumor response and enhance anti-PD-L1 effect,” Dr. Bendell said.
The phase 1 study Dr. Bendell presented, known as GO30103, was designed to evaluate tiragolumab as a single agent and in combination with atezolizumab in advanced solid tumors.
There were 24 patients in the phase 1a portion of GO30103, which was intended to determine the preliminary safety, tolerability, and recommended phase 2 dose of tiragolumab. There were 49 patients treated with tiragolumab plus atezolizumab in the phase 1b portion, which was intended to provide data on pharmacokinetics as well as preliminary antitumor activity of the combination.
No dose-limiting toxicities were seen in either cohort. The recommended phase 2 dose of tiragolumab was 600 mg every 3 weeks.
Tiragolumab was well tolerated in the phase 1a and 1b portions of the trial, according to Dr. Bendell.
“Immune-related adverse events were seen, but their incidence was not out of proportion to events seen with atezolizumab alone,” she said.
Treatment-related grade 3-4 adverse events occurred in one patient (4%) in the phase 1a portion of the trial and two patients (4%) in the phase 1b portion. There were no grade 5 adverse events related to treatment.
Efficacy and next steps
No objective responses were seen with tiragolumab monotherapy, although several patients did exhibit tumor reduction.
“We were not really expecting much single-agent activity of the anti-TIGIT drug,” Dr. Bendell said. “There’s some preclinical data that suggests that TIGIT may be more important as a single agent in earlier stages of cancer.”
In contrast, the combination of tiragolumab and atezolizumab resulted in several responses, including one in a patient with PD-L1-positive NSCLC who was previously treated with immunotherapy, according to Dr. Bendell.
The 13-patient expansion cohort of patients with PD-L1-positive NSCLC were treated at the recommended phase 2 dose of tiragolumab and atezolizumab. In these chemoimmunotherapy-naive patients, the overall response rate was 46%. Responses occurred in 6 of 13 patients and included 2 complete responses. Four patients had stable disease, so the disease control rate was 85% (11/13).
Based on that expansion cohort, a randomized, phase 2 study called CITYSCAPE was initiated. Results of CITYSCAPE were recently presented as part of the American Society of Clinical Oncology virtual scientific program.
In that study, tiragolumab plus atezolizumab improved the overall response rate and progression-free survival when compared with placebo plus atezolizumab. More substantial improvement was seen in the subgroup of patients with PD-L1 tumor proportion scores of 50% or greater.
The activity and safety of tiragolumab plus atezolizumab will be confirmed in the ongoing SKYSCRAPER-01 trial (NCT04294810), a phase 3 study of first-line treatment in patients with NSCLC and a PD-L1 tumor proportion score of 50% or greater, according to investigators.
The phase 1 study presented by Dr. Bendell was sponsored by Genentech. Dr. Bendell disclosed relationships with Genentech/Roche, Gilead, Five Prime, Lilly, and other companies.
SOURCE: Bendell JC et al. AACR 2020, Abstract CT302.
FROM AACR 2020
Treatments linked to death in COVID patients with thoracic cancers
Prior treatment with steroids, anticoagulants, chemotherapy alone, or chemotherapy plus immunotherapy were all associated with an increased risk of death, but prior treatment with tyrosine kinase inhibitors or immunotherapy alone were not.
At the same time, there were no COVID-19–directed treatments that seemed to affect the risk of death.
“When we look at therapies administered to treat COVID-19 … including anticoagulation, antibiotics, antivirals, hydroxychloroquine, we found that no particular therapy was associated with increased chance of recovery from COVID-19,” said Leora Horn, MD, of Vanderbilt-Ingram Cancer Center in Nashville, Tenn.
Dr. Horn presented these findings as part of the American Society of Clinical Oncology virtual scientific program.
About TERAVOLT
The TERAVOLT registry is the brainchild of Marina Garassino, MD, of the National Cancer Institute of Milan. On March 15, Dr. Garassino emailed colleagues around the world with the idea of starting the registry. Within 5 days, the final protocol was approved, and the first patient was entered onto TERAVOLT.
In creating a registry, Dr. Garassino and colleagues wanted to “determine the demographic factors, comorbidities, cancer characteristics, and therapies that place patients with thoracic malignancies who develop COVID-19 most at risk for hospitalization and death,” Dr. Horn said.
Other goals of the registry are “to understand the clinical course of patients with thoracic malignancies who are infected by SARS-CoV-2, to provide practitioners with real-time data on therapeutic strategies that may impact survival, [and] to evaluate the long-term impact on cancer outcomes related to care adjustments and delays in patients with thoracic malignancies,” she added.
Dr. Garassino presented the first analysis of TERAVOLT data at the AACR virtual meeting I in April. Results were recently published in The Lancet Oncology as well. That analysis included 200 patients, 98% of whom were from Europe, and the median follow-up was 15 days.
Baseline characteristics and outcomes
Dr. Horn’s updated analysis included 400 patients with a median follow-up of 33 days from COVID-19 diagnosis. The data encompassed patients from North and South America, Europe, Africa, Asia, and Australia.
Of the 400 patients, 169 had recovered, 141 had died, and 118 were still in the hospital at the time of analysis. In all, 334 patients (78.3%) required a hospital admission, and 33 (8.3%) were admitted to the ICU. The median length of hospitalization was 10 days.
Across the three outcome groups (recovered, died, ongoing), the median age was 67-70 years. Most patients had non–small cell lung cancer (74.5%-81.9%), and most had stage IV disease (61.4%-76.8%).
A majority of patients were male (63.3%-70.2%), and most were current or former smokers (77.5%-86.9%). The median body mass index was 24-25 kg/m2, and 35%-46.4% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0.
Most patients (82.2%-90.7%) had COVID-19 diagnosed via real-time polymerase chain reaction, although some patients were diagnosed via clinical findings alone (3.1%-5%).
“[R]egardless of outcome, the most common presenting symptom was fever, cough, or dyspnea,” Dr. Horn noted.
As for complications of COVID-19, 71% of patients who died had pneumonitis/pneumonia, 49.6% had acute respiratory distress syndrome, 14.9% had multiorgan failure, 12.1% had sepsis, and 5.7% had coagulopathy.
Among recovered patients, 59% had pneumonitis/pneumonia, 4.1% had acute respiratory distress syndrome, 3% had coagulopathy, 0.6% had sepsis, and none had multiorgan failure.
Patients who recovered were more likely to have no comorbidities at baseline, and 31.2% of patients who died had at least one comorbidity. The most frequent comorbidities were hypertension, chronic obstructive pulmonary disease, vascular disease, diabetes, and renal insufficiencies.
Prior treatments and COVID therapy
Among patients who died, 33.4% were on ACE inhibitors or angiotensin II receptor blockers, 27% were on anticoagulants, and 23.4% were on steroids (the equivalent of at least 10 mg of prednisone per day) at the time of COVID-19 diagnosis.
Among recovered patients, 20.7% were on ACE inhibitors or angiotensin II receptor blockers, 18.3% were on anticoagulants, and 14.2% were on steroids at the time of COVID-19 diagnosis.
“When we look at cancer therapy in the last 3 months, we can see that, regardless of outcome, the majority of patients had either not been treated or were on first-line therapy at the time of their COVID-19 diagnosis,” Dr. Horn noted.
Among patients who died, 46.8% had received chemotherapy, 22% had received immunotherapy, 12.8% had received targeted therapy, and 9.2% had received radiotherapy.
Among recovered patients, 33.7% had received chemotherapy, 26.6% had received immunotherapy, 19.5% had received targeted therapy, and 14.2% had received radiotherapy.
COVID-19–directed treatments included anticoagulation, antibiotics, antivirals, antifungals, steroids, interleukin-6 inhibitors, and hydroxychloroquine. Use of these therapies was similar among patients who recovered and patients who died.
Factors associated with death
In all, 79.4% of deaths were attributed to COVID-19, 10.6% were attributed to cancer, 8.5% were attributed to cancer and COVID-19, and 1.4% of deaths had an unknown cause.
In a univariate analysis, baseline characteristics associated with an increased risk of death were age of 65 years or older (P = .0033), one or more comorbidity (P = .0351), and ECOG performance status of 1 (P < .0001). Therapies associated with an increased risk of death in a univariate analysis included steroids (P = .0186), anticoagulation (P = .0562), and either chemotherapy alone or chemotherapy plus immunotherapy (P = .0256).
In a multivariate analysis, age over 65 years (P = .018), ECOG performance status of 1 (P < .001), prior use of steroids (P = .052), and receipt of chemotherapy alone or in combination with immunotherapy (P = .025) were all associated with an increased risk of death.
“There is no impact of gender [sex], body mass index, smoking status, stage, or type of cancer on risk of death,” Dr. Horn said. “Therapy administered to treat COVID-19 is not significantly associated with outcome.”
“The impact of COVID-19 infection on cancer management and outcomes must be evaluated,” she added. “Data collection is ongoing, with additional analysis and studies planned to look at patient and provider perception of COVID-19 and the impact it has had on cancer care.”
Strengths and limitations
There are several limitations to findings from the TERAVOLT registry, according to invited discussant Giuseppe Curigliano, MD, PhD, of the University of Milan.
He said the results are limited by the differences in triage decisions between European and other centers, the fact that most patients in TERAVOLT were hospitalized, the high proportion of patients with stage IV non–small cell lung cancer, and methods of data collection and analysis.
“There is no real-time data capture, no auditing, no standardized outcome definitions, and CRFs [case report forms] had a lot of limitations,” Dr. Curigliano said. “We have multiple biases, including selection bias, recall bias, confounding by indication, and changes in practice or disease evolution.”
Dr. Curigliano noted, however, that TERAVOLT is the largest real-world dataset of patients with COVID-19 and thoracic malignancies.
Furthermore, results from TERAVOLT correspond to results from the CCC-19 registry. Data from both registries suggest that older age, the presence of comorbidities, higher ECOG performances status, and chemotherapy alone or in combination with other therapies are associated with increased mortality among patients with cancer and COVID-19.
The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer. Dr. Horn disclosed relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, and other pharmaceutical companies. Dr. Curigliano disclosed relationships with AstraZeneca, Boehringer Ingelheim, Ellipses Pharma, and other pharmaceutical companies.
SOURCE: Horn L et al. ASCO 2020, Abstract LBA111.
Prior treatment with steroids, anticoagulants, chemotherapy alone, or chemotherapy plus immunotherapy were all associated with an increased risk of death, but prior treatment with tyrosine kinase inhibitors or immunotherapy alone were not.
At the same time, there were no COVID-19–directed treatments that seemed to affect the risk of death.
“When we look at therapies administered to treat COVID-19 … including anticoagulation, antibiotics, antivirals, hydroxychloroquine, we found that no particular therapy was associated with increased chance of recovery from COVID-19,” said Leora Horn, MD, of Vanderbilt-Ingram Cancer Center in Nashville, Tenn.
Dr. Horn presented these findings as part of the American Society of Clinical Oncology virtual scientific program.
About TERAVOLT
The TERAVOLT registry is the brainchild of Marina Garassino, MD, of the National Cancer Institute of Milan. On March 15, Dr. Garassino emailed colleagues around the world with the idea of starting the registry. Within 5 days, the final protocol was approved, and the first patient was entered onto TERAVOLT.
In creating a registry, Dr. Garassino and colleagues wanted to “determine the demographic factors, comorbidities, cancer characteristics, and therapies that place patients with thoracic malignancies who develop COVID-19 most at risk for hospitalization and death,” Dr. Horn said.
Other goals of the registry are “to understand the clinical course of patients with thoracic malignancies who are infected by SARS-CoV-2, to provide practitioners with real-time data on therapeutic strategies that may impact survival, [and] to evaluate the long-term impact on cancer outcomes related to care adjustments and delays in patients with thoracic malignancies,” she added.
Dr. Garassino presented the first analysis of TERAVOLT data at the AACR virtual meeting I in April. Results were recently published in The Lancet Oncology as well. That analysis included 200 patients, 98% of whom were from Europe, and the median follow-up was 15 days.
Baseline characteristics and outcomes
Dr. Horn’s updated analysis included 400 patients with a median follow-up of 33 days from COVID-19 diagnosis. The data encompassed patients from North and South America, Europe, Africa, Asia, and Australia.
Of the 400 patients, 169 had recovered, 141 had died, and 118 were still in the hospital at the time of analysis. In all, 334 patients (78.3%) required a hospital admission, and 33 (8.3%) were admitted to the ICU. The median length of hospitalization was 10 days.
Across the three outcome groups (recovered, died, ongoing), the median age was 67-70 years. Most patients had non–small cell lung cancer (74.5%-81.9%), and most had stage IV disease (61.4%-76.8%).
A majority of patients were male (63.3%-70.2%), and most were current or former smokers (77.5%-86.9%). The median body mass index was 24-25 kg/m2, and 35%-46.4% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0.
Most patients (82.2%-90.7%) had COVID-19 diagnosed via real-time polymerase chain reaction, although some patients were diagnosed via clinical findings alone (3.1%-5%).
“[R]egardless of outcome, the most common presenting symptom was fever, cough, or dyspnea,” Dr. Horn noted.
As for complications of COVID-19, 71% of patients who died had pneumonitis/pneumonia, 49.6% had acute respiratory distress syndrome, 14.9% had multiorgan failure, 12.1% had sepsis, and 5.7% had coagulopathy.
Among recovered patients, 59% had pneumonitis/pneumonia, 4.1% had acute respiratory distress syndrome, 3% had coagulopathy, 0.6% had sepsis, and none had multiorgan failure.
Patients who recovered were more likely to have no comorbidities at baseline, and 31.2% of patients who died had at least one comorbidity. The most frequent comorbidities were hypertension, chronic obstructive pulmonary disease, vascular disease, diabetes, and renal insufficiencies.
Prior treatments and COVID therapy
Among patients who died, 33.4% were on ACE inhibitors or angiotensin II receptor blockers, 27% were on anticoagulants, and 23.4% were on steroids (the equivalent of at least 10 mg of prednisone per day) at the time of COVID-19 diagnosis.
Among recovered patients, 20.7% were on ACE inhibitors or angiotensin II receptor blockers, 18.3% were on anticoagulants, and 14.2% were on steroids at the time of COVID-19 diagnosis.
“When we look at cancer therapy in the last 3 months, we can see that, regardless of outcome, the majority of patients had either not been treated or were on first-line therapy at the time of their COVID-19 diagnosis,” Dr. Horn noted.
Among patients who died, 46.8% had received chemotherapy, 22% had received immunotherapy, 12.8% had received targeted therapy, and 9.2% had received radiotherapy.
Among recovered patients, 33.7% had received chemotherapy, 26.6% had received immunotherapy, 19.5% had received targeted therapy, and 14.2% had received radiotherapy.
COVID-19–directed treatments included anticoagulation, antibiotics, antivirals, antifungals, steroids, interleukin-6 inhibitors, and hydroxychloroquine. Use of these therapies was similar among patients who recovered and patients who died.
Factors associated with death
In all, 79.4% of deaths were attributed to COVID-19, 10.6% were attributed to cancer, 8.5% were attributed to cancer and COVID-19, and 1.4% of deaths had an unknown cause.
In a univariate analysis, baseline characteristics associated with an increased risk of death were age of 65 years or older (P = .0033), one or more comorbidity (P = .0351), and ECOG performance status of 1 (P < .0001). Therapies associated with an increased risk of death in a univariate analysis included steroids (P = .0186), anticoagulation (P = .0562), and either chemotherapy alone or chemotherapy plus immunotherapy (P = .0256).
In a multivariate analysis, age over 65 years (P = .018), ECOG performance status of 1 (P < .001), prior use of steroids (P = .052), and receipt of chemotherapy alone or in combination with immunotherapy (P = .025) were all associated with an increased risk of death.
“There is no impact of gender [sex], body mass index, smoking status, stage, or type of cancer on risk of death,” Dr. Horn said. “Therapy administered to treat COVID-19 is not significantly associated with outcome.”
“The impact of COVID-19 infection on cancer management and outcomes must be evaluated,” she added. “Data collection is ongoing, with additional analysis and studies planned to look at patient and provider perception of COVID-19 and the impact it has had on cancer care.”
Strengths and limitations
There are several limitations to findings from the TERAVOLT registry, according to invited discussant Giuseppe Curigliano, MD, PhD, of the University of Milan.
He said the results are limited by the differences in triage decisions between European and other centers, the fact that most patients in TERAVOLT were hospitalized, the high proportion of patients with stage IV non–small cell lung cancer, and methods of data collection and analysis.
“There is no real-time data capture, no auditing, no standardized outcome definitions, and CRFs [case report forms] had a lot of limitations,” Dr. Curigliano said. “We have multiple biases, including selection bias, recall bias, confounding by indication, and changes in practice or disease evolution.”
Dr. Curigliano noted, however, that TERAVOLT is the largest real-world dataset of patients with COVID-19 and thoracic malignancies.
Furthermore, results from TERAVOLT correspond to results from the CCC-19 registry. Data from both registries suggest that older age, the presence of comorbidities, higher ECOG performances status, and chemotherapy alone or in combination with other therapies are associated with increased mortality among patients with cancer and COVID-19.
The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer. Dr. Horn disclosed relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, and other pharmaceutical companies. Dr. Curigliano disclosed relationships with AstraZeneca, Boehringer Ingelheim, Ellipses Pharma, and other pharmaceutical companies.
SOURCE: Horn L et al. ASCO 2020, Abstract LBA111.
Prior treatment with steroids, anticoagulants, chemotherapy alone, or chemotherapy plus immunotherapy were all associated with an increased risk of death, but prior treatment with tyrosine kinase inhibitors or immunotherapy alone were not.
At the same time, there were no COVID-19–directed treatments that seemed to affect the risk of death.
“When we look at therapies administered to treat COVID-19 … including anticoagulation, antibiotics, antivirals, hydroxychloroquine, we found that no particular therapy was associated with increased chance of recovery from COVID-19,” said Leora Horn, MD, of Vanderbilt-Ingram Cancer Center in Nashville, Tenn.
Dr. Horn presented these findings as part of the American Society of Clinical Oncology virtual scientific program.
About TERAVOLT
The TERAVOLT registry is the brainchild of Marina Garassino, MD, of the National Cancer Institute of Milan. On March 15, Dr. Garassino emailed colleagues around the world with the idea of starting the registry. Within 5 days, the final protocol was approved, and the first patient was entered onto TERAVOLT.
In creating a registry, Dr. Garassino and colleagues wanted to “determine the demographic factors, comorbidities, cancer characteristics, and therapies that place patients with thoracic malignancies who develop COVID-19 most at risk for hospitalization and death,” Dr. Horn said.
Other goals of the registry are “to understand the clinical course of patients with thoracic malignancies who are infected by SARS-CoV-2, to provide practitioners with real-time data on therapeutic strategies that may impact survival, [and] to evaluate the long-term impact on cancer outcomes related to care adjustments and delays in patients with thoracic malignancies,” she added.
Dr. Garassino presented the first analysis of TERAVOLT data at the AACR virtual meeting I in April. Results were recently published in The Lancet Oncology as well. That analysis included 200 patients, 98% of whom were from Europe, and the median follow-up was 15 days.
Baseline characteristics and outcomes
Dr. Horn’s updated analysis included 400 patients with a median follow-up of 33 days from COVID-19 diagnosis. The data encompassed patients from North and South America, Europe, Africa, Asia, and Australia.
Of the 400 patients, 169 had recovered, 141 had died, and 118 were still in the hospital at the time of analysis. In all, 334 patients (78.3%) required a hospital admission, and 33 (8.3%) were admitted to the ICU. The median length of hospitalization was 10 days.
Across the three outcome groups (recovered, died, ongoing), the median age was 67-70 years. Most patients had non–small cell lung cancer (74.5%-81.9%), and most had stage IV disease (61.4%-76.8%).
A majority of patients were male (63.3%-70.2%), and most were current or former smokers (77.5%-86.9%). The median body mass index was 24-25 kg/m2, and 35%-46.4% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0.
Most patients (82.2%-90.7%) had COVID-19 diagnosed via real-time polymerase chain reaction, although some patients were diagnosed via clinical findings alone (3.1%-5%).
“[R]egardless of outcome, the most common presenting symptom was fever, cough, or dyspnea,” Dr. Horn noted.
As for complications of COVID-19, 71% of patients who died had pneumonitis/pneumonia, 49.6% had acute respiratory distress syndrome, 14.9% had multiorgan failure, 12.1% had sepsis, and 5.7% had coagulopathy.
Among recovered patients, 59% had pneumonitis/pneumonia, 4.1% had acute respiratory distress syndrome, 3% had coagulopathy, 0.6% had sepsis, and none had multiorgan failure.
Patients who recovered were more likely to have no comorbidities at baseline, and 31.2% of patients who died had at least one comorbidity. The most frequent comorbidities were hypertension, chronic obstructive pulmonary disease, vascular disease, diabetes, and renal insufficiencies.
Prior treatments and COVID therapy
Among patients who died, 33.4% were on ACE inhibitors or angiotensin II receptor blockers, 27% were on anticoagulants, and 23.4% were on steroids (the equivalent of at least 10 mg of prednisone per day) at the time of COVID-19 diagnosis.
Among recovered patients, 20.7% were on ACE inhibitors or angiotensin II receptor blockers, 18.3% were on anticoagulants, and 14.2% were on steroids at the time of COVID-19 diagnosis.
“When we look at cancer therapy in the last 3 months, we can see that, regardless of outcome, the majority of patients had either not been treated or were on first-line therapy at the time of their COVID-19 diagnosis,” Dr. Horn noted.
Among patients who died, 46.8% had received chemotherapy, 22% had received immunotherapy, 12.8% had received targeted therapy, and 9.2% had received radiotherapy.
Among recovered patients, 33.7% had received chemotherapy, 26.6% had received immunotherapy, 19.5% had received targeted therapy, and 14.2% had received radiotherapy.
COVID-19–directed treatments included anticoagulation, antibiotics, antivirals, antifungals, steroids, interleukin-6 inhibitors, and hydroxychloroquine. Use of these therapies was similar among patients who recovered and patients who died.
Factors associated with death
In all, 79.4% of deaths were attributed to COVID-19, 10.6% were attributed to cancer, 8.5% were attributed to cancer and COVID-19, and 1.4% of deaths had an unknown cause.
In a univariate analysis, baseline characteristics associated with an increased risk of death were age of 65 years or older (P = .0033), one or more comorbidity (P = .0351), and ECOG performance status of 1 (P < .0001). Therapies associated with an increased risk of death in a univariate analysis included steroids (P = .0186), anticoagulation (P = .0562), and either chemotherapy alone or chemotherapy plus immunotherapy (P = .0256).
In a multivariate analysis, age over 65 years (P = .018), ECOG performance status of 1 (P < .001), prior use of steroids (P = .052), and receipt of chemotherapy alone or in combination with immunotherapy (P = .025) were all associated with an increased risk of death.
“There is no impact of gender [sex], body mass index, smoking status, stage, or type of cancer on risk of death,” Dr. Horn said. “Therapy administered to treat COVID-19 is not significantly associated with outcome.”
“The impact of COVID-19 infection on cancer management and outcomes must be evaluated,” she added. “Data collection is ongoing, with additional analysis and studies planned to look at patient and provider perception of COVID-19 and the impact it has had on cancer care.”
Strengths and limitations
There are several limitations to findings from the TERAVOLT registry, according to invited discussant Giuseppe Curigliano, MD, PhD, of the University of Milan.
He said the results are limited by the differences in triage decisions between European and other centers, the fact that most patients in TERAVOLT were hospitalized, the high proportion of patients with stage IV non–small cell lung cancer, and methods of data collection and analysis.
“There is no real-time data capture, no auditing, no standardized outcome definitions, and CRFs [case report forms] had a lot of limitations,” Dr. Curigliano said. “We have multiple biases, including selection bias, recall bias, confounding by indication, and changes in practice or disease evolution.”
Dr. Curigliano noted, however, that TERAVOLT is the largest real-world dataset of patients with COVID-19 and thoracic malignancies.
Furthermore, results from TERAVOLT correspond to results from the CCC-19 registry. Data from both registries suggest that older age, the presence of comorbidities, higher ECOG performances status, and chemotherapy alone or in combination with other therapies are associated with increased mortality among patients with cancer and COVID-19.
The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer. Dr. Horn disclosed relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, and other pharmaceutical companies. Dr. Curigliano disclosed relationships with AstraZeneca, Boehringer Ingelheim, Ellipses Pharma, and other pharmaceutical companies.
SOURCE: Horn L et al. ASCO 2020, Abstract LBA111.
FROM ASCO 2020
Personalized cancer vaccine may enhance checkpoint inhibitor activity
Combining a personalized cancer vaccine with an immune checkpoint inhibitor induced neoantigen-specific immune responses in most patients with advanced solid tumors in a phase 1b study.
Only two clinical responses were seen in this early investigation of the vaccine, RO7198457, combined with the PD-L1 inhibitor atezolizumab. However, T-cell responses were observed in about three-quarters of the patients evaluated, according to study investigator Juanita Lopez, MB BChir, PhD.
Those immune responses, coupled with preliminary evidence of infiltration of RO7198457-stimulated T cells into tumors, suggest the viability of this individualized anticancer strategy, according to Dr. Lopez, a consultant medical oncologist at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London.
“Failure of T-cell priming is a major cause of lack of response to immune checkpoint inhibitors,” Dr. Lopez said in an interview. “We hoped that, by eliciting a tumor-specific T-cell response, we would be able to overcome this.”
Preclinical data suggested the combination of vaccine and immune checkpoint inhibitors improved outcomes, which prompted the current study, added Dr. Lopez, who presented results from this study at the American Association for Cancer Research virtual meeting II.
Dr. Lopez noted that mutated neoantigens are recognized as foreign and have been shown to induce stronger T-cell responses, compared with shared antigens, likely because of a lack of central tolerance.
“Most of these mutated neoantigens are not shared between the patients, and therefore, targeted neoantigen-specific therapy requires an individualized approach,” she explained.
RO7198457 is manufactured on a per-patient basis and includes as many as 20 tumor-specific neoepitopes.
Study details
Dr. Lopez presented results from dose-escalation and expansion cohorts of the study, which included 142 patients with advanced solid tumors. The patients had colorectal, skin, kidney, lung, urothelial, breast, gynecologic, and head and neck cancers.
Most patients had low or no PD-L1 expression, and nearly 40% had received prior treatment with a checkpoint inhibitor.
Patients received nine doses of RO7198457 at 25-50 mcg during the 12-week induction stage. They then received RO7198457 every eight cycles until disease progression. Patients received atezolizumab at 1,200 mg on day 1 of each 21-day cycle.
Induction of proinflammatory cytokines was observed at each dose tested, and ex vivo T-cell responses were noted in 46 of 63 patients evaluated, or 73%.
T-cell receptors specific to RO7198457 were present posttreatment in a patient with rectal cancer, providing some preliminary evidence suggesting infiltration of RO7198457-stimulated T cells in the tumor, Dr. Lopez said.
There were two clinical responses. A patient with rectal cancer had a complete response, and a patient with triple-negative breast cancer had a partial response.
The combination of RO7198457 with atezolizumab was generally well tolerated, and the maximum tolerated dose was not reached, Dr. Lopez said. Most adverse events were grade 1/2, and immune-mediated adverse events were rare.
Implications and next steps
This study furthers earlier observations from neoantigen vaccine studies by linking dosing of the vaccine to dosing with immune checkpoint inhibitor, rather than giving the vaccine in the period leading up to immune checkpoint inhibitor administration, according to former AACR President Elaine R. Mardis, PhD, of Nationwide Children’s Hospital and The Ohio State University College of Medicine, both in Columbus.
That said, the implications for clinical practice remain unclear, according to Dr. Mardis.
“This combination did elicit an immune response that was highly specific for the neoantigen vaccine, but most patients did not receive a clinical benefit of disease response,” Dr. Mardis said in an interview. “This tells us the combination approach used was, overall, not quite right, and we need to continue to innovate in this area.”
The low clinical response rate in the study was likely caused in part by the fact that patients had very advanced disease and were heavily pretreated, according to Dr. Lopez
Randomized phase 2 studies of RO7198457 are now underway, Dr. Lopez said. One is a study of RO7198457 plus atezolizumab as adjuvant treatment for non–small cell lung cancer (NCT04267237). Another is testing RO7198457 in combination with pembrolizumab as first-line treatment for melanoma (NCT03815058).
The current study was funded by Genentech and BioNTech. Dr. Lopez reported disclosures related to Roche/Genentech, Basilea Pharmaceutica, and Genmab. Dr. Mardis reported disclosures related to Quiagen NV, PACT Pharma, Kiadis Pharma NV, and Interpreta.
SOURCE: Lopez J et al. AACR 2020, Abstract CT301.
Combining a personalized cancer vaccine with an immune checkpoint inhibitor induced neoantigen-specific immune responses in most patients with advanced solid tumors in a phase 1b study.
Only two clinical responses were seen in this early investigation of the vaccine, RO7198457, combined with the PD-L1 inhibitor atezolizumab. However, T-cell responses were observed in about three-quarters of the patients evaluated, according to study investigator Juanita Lopez, MB BChir, PhD.
Those immune responses, coupled with preliminary evidence of infiltration of RO7198457-stimulated T cells into tumors, suggest the viability of this individualized anticancer strategy, according to Dr. Lopez, a consultant medical oncologist at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London.
“Failure of T-cell priming is a major cause of lack of response to immune checkpoint inhibitors,” Dr. Lopez said in an interview. “We hoped that, by eliciting a tumor-specific T-cell response, we would be able to overcome this.”
Preclinical data suggested the combination of vaccine and immune checkpoint inhibitors improved outcomes, which prompted the current study, added Dr. Lopez, who presented results from this study at the American Association for Cancer Research virtual meeting II.
Dr. Lopez noted that mutated neoantigens are recognized as foreign and have been shown to induce stronger T-cell responses, compared with shared antigens, likely because of a lack of central tolerance.
“Most of these mutated neoantigens are not shared between the patients, and therefore, targeted neoantigen-specific therapy requires an individualized approach,” she explained.
RO7198457 is manufactured on a per-patient basis and includes as many as 20 tumor-specific neoepitopes.
Study details
Dr. Lopez presented results from dose-escalation and expansion cohorts of the study, which included 142 patients with advanced solid tumors. The patients had colorectal, skin, kidney, lung, urothelial, breast, gynecologic, and head and neck cancers.
Most patients had low or no PD-L1 expression, and nearly 40% had received prior treatment with a checkpoint inhibitor.
Patients received nine doses of RO7198457 at 25-50 mcg during the 12-week induction stage. They then received RO7198457 every eight cycles until disease progression. Patients received atezolizumab at 1,200 mg on day 1 of each 21-day cycle.
Induction of proinflammatory cytokines was observed at each dose tested, and ex vivo T-cell responses were noted in 46 of 63 patients evaluated, or 73%.
T-cell receptors specific to RO7198457 were present posttreatment in a patient with rectal cancer, providing some preliminary evidence suggesting infiltration of RO7198457-stimulated T cells in the tumor, Dr. Lopez said.
There were two clinical responses. A patient with rectal cancer had a complete response, and a patient with triple-negative breast cancer had a partial response.
The combination of RO7198457 with atezolizumab was generally well tolerated, and the maximum tolerated dose was not reached, Dr. Lopez said. Most adverse events were grade 1/2, and immune-mediated adverse events were rare.
Implications and next steps
This study furthers earlier observations from neoantigen vaccine studies by linking dosing of the vaccine to dosing with immune checkpoint inhibitor, rather than giving the vaccine in the period leading up to immune checkpoint inhibitor administration, according to former AACR President Elaine R. Mardis, PhD, of Nationwide Children’s Hospital and The Ohio State University College of Medicine, both in Columbus.
That said, the implications for clinical practice remain unclear, according to Dr. Mardis.
“This combination did elicit an immune response that was highly specific for the neoantigen vaccine, but most patients did not receive a clinical benefit of disease response,” Dr. Mardis said in an interview. “This tells us the combination approach used was, overall, not quite right, and we need to continue to innovate in this area.”
The low clinical response rate in the study was likely caused in part by the fact that patients had very advanced disease and were heavily pretreated, according to Dr. Lopez
Randomized phase 2 studies of RO7198457 are now underway, Dr. Lopez said. One is a study of RO7198457 plus atezolizumab as adjuvant treatment for non–small cell lung cancer (NCT04267237). Another is testing RO7198457 in combination with pembrolizumab as first-line treatment for melanoma (NCT03815058).
The current study was funded by Genentech and BioNTech. Dr. Lopez reported disclosures related to Roche/Genentech, Basilea Pharmaceutica, and Genmab. Dr. Mardis reported disclosures related to Quiagen NV, PACT Pharma, Kiadis Pharma NV, and Interpreta.
SOURCE: Lopez J et al. AACR 2020, Abstract CT301.
Combining a personalized cancer vaccine with an immune checkpoint inhibitor induced neoantigen-specific immune responses in most patients with advanced solid tumors in a phase 1b study.
Only two clinical responses were seen in this early investigation of the vaccine, RO7198457, combined with the PD-L1 inhibitor atezolizumab. However, T-cell responses were observed in about three-quarters of the patients evaluated, according to study investigator Juanita Lopez, MB BChir, PhD.
Those immune responses, coupled with preliminary evidence of infiltration of RO7198457-stimulated T cells into tumors, suggest the viability of this individualized anticancer strategy, according to Dr. Lopez, a consultant medical oncologist at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London.
“Failure of T-cell priming is a major cause of lack of response to immune checkpoint inhibitors,” Dr. Lopez said in an interview. “We hoped that, by eliciting a tumor-specific T-cell response, we would be able to overcome this.”
Preclinical data suggested the combination of vaccine and immune checkpoint inhibitors improved outcomes, which prompted the current study, added Dr. Lopez, who presented results from this study at the American Association for Cancer Research virtual meeting II.
Dr. Lopez noted that mutated neoantigens are recognized as foreign and have been shown to induce stronger T-cell responses, compared with shared antigens, likely because of a lack of central tolerance.
“Most of these mutated neoantigens are not shared between the patients, and therefore, targeted neoantigen-specific therapy requires an individualized approach,” she explained.
RO7198457 is manufactured on a per-patient basis and includes as many as 20 tumor-specific neoepitopes.
Study details
Dr. Lopez presented results from dose-escalation and expansion cohorts of the study, which included 142 patients with advanced solid tumors. The patients had colorectal, skin, kidney, lung, urothelial, breast, gynecologic, and head and neck cancers.
Most patients had low or no PD-L1 expression, and nearly 40% had received prior treatment with a checkpoint inhibitor.
Patients received nine doses of RO7198457 at 25-50 mcg during the 12-week induction stage. They then received RO7198457 every eight cycles until disease progression. Patients received atezolizumab at 1,200 mg on day 1 of each 21-day cycle.
Induction of proinflammatory cytokines was observed at each dose tested, and ex vivo T-cell responses were noted in 46 of 63 patients evaluated, or 73%.
T-cell receptors specific to RO7198457 were present posttreatment in a patient with rectal cancer, providing some preliminary evidence suggesting infiltration of RO7198457-stimulated T cells in the tumor, Dr. Lopez said.
There were two clinical responses. A patient with rectal cancer had a complete response, and a patient with triple-negative breast cancer had a partial response.
The combination of RO7198457 with atezolizumab was generally well tolerated, and the maximum tolerated dose was not reached, Dr. Lopez said. Most adverse events were grade 1/2, and immune-mediated adverse events were rare.
Implications and next steps
This study furthers earlier observations from neoantigen vaccine studies by linking dosing of the vaccine to dosing with immune checkpoint inhibitor, rather than giving the vaccine in the period leading up to immune checkpoint inhibitor administration, according to former AACR President Elaine R. Mardis, PhD, of Nationwide Children’s Hospital and The Ohio State University College of Medicine, both in Columbus.
That said, the implications for clinical practice remain unclear, according to Dr. Mardis.
“This combination did elicit an immune response that was highly specific for the neoantigen vaccine, but most patients did not receive a clinical benefit of disease response,” Dr. Mardis said in an interview. “This tells us the combination approach used was, overall, not quite right, and we need to continue to innovate in this area.”
The low clinical response rate in the study was likely caused in part by the fact that patients had very advanced disease and were heavily pretreated, according to Dr. Lopez
Randomized phase 2 studies of RO7198457 are now underway, Dr. Lopez said. One is a study of RO7198457 plus atezolizumab as adjuvant treatment for non–small cell lung cancer (NCT04267237). Another is testing RO7198457 in combination with pembrolizumab as first-line treatment for melanoma (NCT03815058).
The current study was funded by Genentech and BioNTech. Dr. Lopez reported disclosures related to Roche/Genentech, Basilea Pharmaceutica, and Genmab. Dr. Mardis reported disclosures related to Quiagen NV, PACT Pharma, Kiadis Pharma NV, and Interpreta.
SOURCE: Lopez J et al. AACR 2020, Abstract CT301.
FROM AACR 2020
Highlights in Non–Small Cell Lung Cancer From ASCO 2020
Presented during the ASCO 2020 plenary session, the results of the phase 3 ADAURA trial will prove practice-changing, according to Dr. Mark Kris of Memorial Sloan Kettering Cancer Center. Over 600 patients whose resected tumors were found to have EGFR mutations were treated with osimertinib. The results more than doubled disease-free survival rates, from 44% to 90% at 2 years.
Among other adjuvant trials, the phase 2 VISION study looked at tepotinib, a once-daily, highly selective oral MET inhibitor. The study showed durable responses coupled with acceptable side effects. The drug has been given fast-track status by the US Food and Drug Administration.
Dr. Kris notes that the DESTINY study introduces trastuzumab deruxtecan, an antibody-drug conjugate, as a promising new class of drugs for lung cancer patients. Interim results presented at ASCO further support the HER2 mutation as another potential target for patients with lung cancer.
Finally, the phase 2 CITYSCAPE study provides preliminary evidence for a new checkpoint inhibitor. The monoclonal antibody tiragolumab was developed to block TIGIT. The study showed that the combination of tiragolumab and atezolizumab can improve both rates of response and time to disease recurrence — results Dr. Kris considers encouraging for patients with advanced lung cancer.
Mark G. Kris, MD
Mark G. Kris, MD, Professor, Department of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Presented during the ASCO 2020 plenary session, the results of the phase 3 ADAURA trial will prove practice-changing, according to Dr. Mark Kris of Memorial Sloan Kettering Cancer Center. Over 600 patients whose resected tumors were found to have EGFR mutations were treated with osimertinib. The results more than doubled disease-free survival rates, from 44% to 90% at 2 years.
Among other adjuvant trials, the phase 2 VISION study looked at tepotinib, a once-daily, highly selective oral MET inhibitor. The study showed durable responses coupled with acceptable side effects. The drug has been given fast-track status by the US Food and Drug Administration.
Dr. Kris notes that the DESTINY study introduces trastuzumab deruxtecan, an antibody-drug conjugate, as a promising new class of drugs for lung cancer patients. Interim results presented at ASCO further support the HER2 mutation as another potential target for patients with lung cancer.
Finally, the phase 2 CITYSCAPE study provides preliminary evidence for a new checkpoint inhibitor. The monoclonal antibody tiragolumab was developed to block TIGIT. The study showed that the combination of tiragolumab and atezolizumab can improve both rates of response and time to disease recurrence — results Dr. Kris considers encouraging for patients with advanced lung cancer.
Mark G. Kris, MD
Mark G. Kris, MD, Professor, Department of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Presented during the ASCO 2020 plenary session, the results of the phase 3 ADAURA trial will prove practice-changing, according to Dr. Mark Kris of Memorial Sloan Kettering Cancer Center. Over 600 patients whose resected tumors were found to have EGFR mutations were treated with osimertinib. The results more than doubled disease-free survival rates, from 44% to 90% at 2 years.
Among other adjuvant trials, the phase 2 VISION study looked at tepotinib, a once-daily, highly selective oral MET inhibitor. The study showed durable responses coupled with acceptable side effects. The drug has been given fast-track status by the US Food and Drug Administration.
Dr. Kris notes that the DESTINY study introduces trastuzumab deruxtecan, an antibody-drug conjugate, as a promising new class of drugs for lung cancer patients. Interim results presented at ASCO further support the HER2 mutation as another potential target for patients with lung cancer.
Finally, the phase 2 CITYSCAPE study provides preliminary evidence for a new checkpoint inhibitor. The monoclonal antibody tiragolumab was developed to block TIGIT. The study showed that the combination of tiragolumab and atezolizumab can improve both rates of response and time to disease recurrence — results Dr. Kris considers encouraging for patients with advanced lung cancer.
Mark G. Kris, MD
Mark G. Kris, MD, Professor, Department of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
