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Pembrolizumab proves promising for treating advanced SCLC
VIENNA – One third of patients with extensive-stage small-cell lung cancer (SCLC) treated with the checkpoint inhibitor pembrolizumab achieved an objective response, according to updated data from the KEYNOTE-28 trial.
Of the 24 patients with advanced SCLC who received pembrolizumab in the multicohort phase Ib study, one had a complete response, seven had a partial response, and one further patient had stable disease for 6 or more months, giving a clinical benefit rate of 33.3% (95% CI, 15.6-53.3%).
“Pembrolizumab demonstrated meaningful antitumor activity in previously treated patients with PD-L1-positive small-cell lung cancer,” said presenting study author Patrick A. Ott, MD, PhD, of the Dana-Faber Cancer Institute in Boston.
“Responses were durable, with a median duration of response of 19.4 months,” Dr. Ott said at the World Conference on Cancer, which is sponsored by the International Association for the Study of Lung Cancer. About 40% of patients exhibited a decrease in tumor size, he added.
Treatment with pembrolizumab was associated with a progression-free survival (PFS) of 1.2 months, with a range of 1.7-5.9 months. The 6- and 12-month PFS rates were 28.6% and 23.8%, respectively.
The median overall survival (OS) was 9.7 months, ranging from 4.1 months to an upper limit that has not yet been reached. The respective 6- and 12-month OS rates were 66.0% and 37.7%.
“The safety experience was consistent with previous experience for pembrolizumab in other tumor types, and was identical with longer follow-up” Dr. Ott said.
Over a median follow-up duration of 9.8 months, treatment-related adverse events occurred in two-thirds of patients, with arthralgia, asthenia, and rash reported by four (16.7%) patients each, and diarrhea and fatigue by three (12.5%) patients each. There were no cases of pneumonitis.
The mean age of patients recruited into the KEYNOTE-28 trial was 60.5 years; more than half of the patients (58%) were male. Five (20.8%) had stable brain metastases, and 95.8% had small cell histology.
All recruited patients had received prior standard-of-care chemotherapy with cisplatin or carboplatin plus etoposide, 45.8% had received irinotecan or topotecan, and 29.2% had been treated with a taxane. In addition, one patient had received prior radiotherapy, one had been given an investigational tyrosine kinase inhibitor therapy, and another had received another, unspecified, investigational treatment.
After enrollment, all patients were treated with pembrolizumab at an intravenous dose of 10 mg/kg every 2 weeks. Response was assessed every 8 weeks for the first 6 months and then annually, with patients continuing to respond continuing to be treated for up to 2 years or until progression or unacceptable toxicity.
There are two ongoing, phase II trials with pembrolizumab in patients with advanced SCLC. One is looking at maintenance therapy with pembrolizumab after combination chemotherapy and is sponsored by the Barbara Ann Karmanos Cancer Institute in collaboration with the National Cancer Institute (NCT02359019). The other, the REACTION trial sponsored by the European Organisation for Research and Treatment of Cancer, is looking at the use of pembrolizumab together with etoposide and platinum chemotherapy in previously untreated patients (NCT02580994).
Merck funded the KEYNOTE-28 study. Dr. Ott disclosed ties with Bristol-Myers Squibb, Merck, ArmoBiosciences, AstraZeneca/MedImmune, Celldex, Genentech, Alexion, and CytomX.
VIENNA – One third of patients with extensive-stage small-cell lung cancer (SCLC) treated with the checkpoint inhibitor pembrolizumab achieved an objective response, according to updated data from the KEYNOTE-28 trial.
Of the 24 patients with advanced SCLC who received pembrolizumab in the multicohort phase Ib study, one had a complete response, seven had a partial response, and one further patient had stable disease for 6 or more months, giving a clinical benefit rate of 33.3% (95% CI, 15.6-53.3%).
“Pembrolizumab demonstrated meaningful antitumor activity in previously treated patients with PD-L1-positive small-cell lung cancer,” said presenting study author Patrick A. Ott, MD, PhD, of the Dana-Faber Cancer Institute in Boston.
“Responses were durable, with a median duration of response of 19.4 months,” Dr. Ott said at the World Conference on Cancer, which is sponsored by the International Association for the Study of Lung Cancer. About 40% of patients exhibited a decrease in tumor size, he added.
Treatment with pembrolizumab was associated with a progression-free survival (PFS) of 1.2 months, with a range of 1.7-5.9 months. The 6- and 12-month PFS rates were 28.6% and 23.8%, respectively.
The median overall survival (OS) was 9.7 months, ranging from 4.1 months to an upper limit that has not yet been reached. The respective 6- and 12-month OS rates were 66.0% and 37.7%.
“The safety experience was consistent with previous experience for pembrolizumab in other tumor types, and was identical with longer follow-up” Dr. Ott said.
Over a median follow-up duration of 9.8 months, treatment-related adverse events occurred in two-thirds of patients, with arthralgia, asthenia, and rash reported by four (16.7%) patients each, and diarrhea and fatigue by three (12.5%) patients each. There were no cases of pneumonitis.
The mean age of patients recruited into the KEYNOTE-28 trial was 60.5 years; more than half of the patients (58%) were male. Five (20.8%) had stable brain metastases, and 95.8% had small cell histology.
All recruited patients had received prior standard-of-care chemotherapy with cisplatin or carboplatin plus etoposide, 45.8% had received irinotecan or topotecan, and 29.2% had been treated with a taxane. In addition, one patient had received prior radiotherapy, one had been given an investigational tyrosine kinase inhibitor therapy, and another had received another, unspecified, investigational treatment.
After enrollment, all patients were treated with pembrolizumab at an intravenous dose of 10 mg/kg every 2 weeks. Response was assessed every 8 weeks for the first 6 months and then annually, with patients continuing to respond continuing to be treated for up to 2 years or until progression or unacceptable toxicity.
There are two ongoing, phase II trials with pembrolizumab in patients with advanced SCLC. One is looking at maintenance therapy with pembrolizumab after combination chemotherapy and is sponsored by the Barbara Ann Karmanos Cancer Institute in collaboration with the National Cancer Institute (NCT02359019). The other, the REACTION trial sponsored by the European Organisation for Research and Treatment of Cancer, is looking at the use of pembrolizumab together with etoposide and platinum chemotherapy in previously untreated patients (NCT02580994).
Merck funded the KEYNOTE-28 study. Dr. Ott disclosed ties with Bristol-Myers Squibb, Merck, ArmoBiosciences, AstraZeneca/MedImmune, Celldex, Genentech, Alexion, and CytomX.
VIENNA – One third of patients with extensive-stage small-cell lung cancer (SCLC) treated with the checkpoint inhibitor pembrolizumab achieved an objective response, according to updated data from the KEYNOTE-28 trial.
Of the 24 patients with advanced SCLC who received pembrolizumab in the multicohort phase Ib study, one had a complete response, seven had a partial response, and one further patient had stable disease for 6 or more months, giving a clinical benefit rate of 33.3% (95% CI, 15.6-53.3%).
“Pembrolizumab demonstrated meaningful antitumor activity in previously treated patients with PD-L1-positive small-cell lung cancer,” said presenting study author Patrick A. Ott, MD, PhD, of the Dana-Faber Cancer Institute in Boston.
“Responses were durable, with a median duration of response of 19.4 months,” Dr. Ott said at the World Conference on Cancer, which is sponsored by the International Association for the Study of Lung Cancer. About 40% of patients exhibited a decrease in tumor size, he added.
Treatment with pembrolizumab was associated with a progression-free survival (PFS) of 1.2 months, with a range of 1.7-5.9 months. The 6- and 12-month PFS rates were 28.6% and 23.8%, respectively.
The median overall survival (OS) was 9.7 months, ranging from 4.1 months to an upper limit that has not yet been reached. The respective 6- and 12-month OS rates were 66.0% and 37.7%.
“The safety experience was consistent with previous experience for pembrolizumab in other tumor types, and was identical with longer follow-up” Dr. Ott said.
Over a median follow-up duration of 9.8 months, treatment-related adverse events occurred in two-thirds of patients, with arthralgia, asthenia, and rash reported by four (16.7%) patients each, and diarrhea and fatigue by three (12.5%) patients each. There were no cases of pneumonitis.
The mean age of patients recruited into the KEYNOTE-28 trial was 60.5 years; more than half of the patients (58%) were male. Five (20.8%) had stable brain metastases, and 95.8% had small cell histology.
All recruited patients had received prior standard-of-care chemotherapy with cisplatin or carboplatin plus etoposide, 45.8% had received irinotecan or topotecan, and 29.2% had been treated with a taxane. In addition, one patient had received prior radiotherapy, one had been given an investigational tyrosine kinase inhibitor therapy, and another had received another, unspecified, investigational treatment.
After enrollment, all patients were treated with pembrolizumab at an intravenous dose of 10 mg/kg every 2 weeks. Response was assessed every 8 weeks for the first 6 months and then annually, with patients continuing to respond continuing to be treated for up to 2 years or until progression or unacceptable toxicity.
There are two ongoing, phase II trials with pembrolizumab in patients with advanced SCLC. One is looking at maintenance therapy with pembrolizumab after combination chemotherapy and is sponsored by the Barbara Ann Karmanos Cancer Institute in collaboration with the National Cancer Institute (NCT02359019). The other, the REACTION trial sponsored by the European Organisation for Research and Treatment of Cancer, is looking at the use of pembrolizumab together with etoposide and platinum chemotherapy in previously untreated patients (NCT02580994).
Merck funded the KEYNOTE-28 study. Dr. Ott disclosed ties with Bristol-Myers Squibb, Merck, ArmoBiosciences, AstraZeneca/MedImmune, Celldex, Genentech, Alexion, and CytomX.
AT WCLC 2016
Key clinical point: Pembrolizumab has antitumor activity in patients with advanced small-cell lung cancer.
Major finding: The objective response rate was 33.3% (95% CI 15.6-55.3%), including one complete and seven partial responses.
Data source: Phase Ib, nonrandomized, multicohort trial of 24 heavily pretreated patients with extensive-disease small-cell lung cancer.
Disclosures: Merck funded the study. Dr. Ott disclosed ties with Bristol-Myers Squibb, Merck, ArmoBiosciences, AstraZeneca/MedImmune, Celldex, Genentech, Alexion, and CytomX.
VIDEO: Pivotal results nail osimertinib’s role in NSCLC
VIENNA – Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor that received U.S. marketing approval in November 2015 as second-line treatment for selected patients with non–small-cell lung cancer based on phase II trial data, now has the pivotal-trial results that completely justify that action.
During a median follow-up of just over 8 months, patients who had progressed on their first-line EGFR tyrosine kinase inhibitor (TKI) and carried the T790M mutation and switched to osimertinib (Tagrisso) had “overwhelmingly” better response rates and progression-free survival, compared with patients put on standard-of-care chemotherapy in a multicenter randomized trial involving 419 patients, Vassiliki A. Papadimitrakopoulou, MD, reported at the World Conference on Lung Cancer.
The AZD9291 Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (AURA3) trial enrolled 419 patients at 126 international sites during 2014 and 2015. The trial’s primary endpoint was investigator-assessed progression-free survival, which occurred after a median of 10.1 months with osimertinib and 4.4 months with standard chemotherapy, a statistically significant 70% relative risk reduction (P less than .001) in the hazard for death or progressive disease. The drug was as effective for patients with central nervous system metastases as it was for the other patients, which Dr. Papadimitrakopoulou attributed to osimertinib’s good penetration across the blood-brain barrier. The drug’s overall performance in AURA3 was completely consistent with the results of earlier studies that led to its U.S. approval.
Despite that approval, routine testing for T790M mutations and routine prescribing of osimertinib to positive patients “has not fully penetrated U.S. practice,” Dr. Papadimitrakopoulou said, but she hoped that these new confirmatory data will now firmly establish it as standard of care for the tested population.
Osimertinib is now under testing as first-line TKI treatment for EGFR-positive NSCLC regardless of the tumor’s T790M status. It’s going head to head with two first-generation EGFR TKIs, gefitinib and erlotinib, in the FLAURA trial, which should have reportable results in 2017. “We are very encouraged by the AURA3 data that osimertinib could beat the first-generation TKIs” for first-line treatment, she said.
AURA3 was sponsored by AstraZeneca, which markets osimertinib (Tagrisso). Dr. Papadimitrakopoulou is a consultant to, and has received research support from, AstraZeneca and several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
Osimertinib overcomes the T790M mutation, which is the cause of about half of the non–small-cell lung cancers that are EGFR positive and develop resistance to a first- or-second generation tyrosine kinase inhibitor. The AURA3 results officially make osimertinib the standard of care for these patients.
Osimertinib’s performance in AURA3 was consistent with what it did in the earlier studies, producing an overall response rate of about 60%-70% and extending progression-free survival out to a median of 10-11 months.
Tetsuya Mitsudomi, MD, is professor of thoracic surgery at Kindai University in Osaka-Sayama, Japan. He has been a consultant to, and has received honoraria and research support from, AstraZeneca and several other companies. He was principal investigator for AURA2, one of the phase II studies of osimertinib. He made these comments as designated discussant for AURA3.
Osimertinib overcomes the T790M mutation, which is the cause of about half of the non–small-cell lung cancers that are EGFR positive and develop resistance to a first- or-second generation tyrosine kinase inhibitor. The AURA3 results officially make osimertinib the standard of care for these patients.
Osimertinib’s performance in AURA3 was consistent with what it did in the earlier studies, producing an overall response rate of about 60%-70% and extending progression-free survival out to a median of 10-11 months.
Tetsuya Mitsudomi, MD, is professor of thoracic surgery at Kindai University in Osaka-Sayama, Japan. He has been a consultant to, and has received honoraria and research support from, AstraZeneca and several other companies. He was principal investigator for AURA2, one of the phase II studies of osimertinib. He made these comments as designated discussant for AURA3.
Osimertinib overcomes the T790M mutation, which is the cause of about half of the non–small-cell lung cancers that are EGFR positive and develop resistance to a first- or-second generation tyrosine kinase inhibitor. The AURA3 results officially make osimertinib the standard of care for these patients.
Osimertinib’s performance in AURA3 was consistent with what it did in the earlier studies, producing an overall response rate of about 60%-70% and extending progression-free survival out to a median of 10-11 months.
Tetsuya Mitsudomi, MD, is professor of thoracic surgery at Kindai University in Osaka-Sayama, Japan. He has been a consultant to, and has received honoraria and research support from, AstraZeneca and several other companies. He was principal investigator for AURA2, one of the phase II studies of osimertinib. He made these comments as designated discussant for AURA3.
VIENNA – Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor that received U.S. marketing approval in November 2015 as second-line treatment for selected patients with non–small-cell lung cancer based on phase II trial data, now has the pivotal-trial results that completely justify that action.
During a median follow-up of just over 8 months, patients who had progressed on their first-line EGFR tyrosine kinase inhibitor (TKI) and carried the T790M mutation and switched to osimertinib (Tagrisso) had “overwhelmingly” better response rates and progression-free survival, compared with patients put on standard-of-care chemotherapy in a multicenter randomized trial involving 419 patients, Vassiliki A. Papadimitrakopoulou, MD, reported at the World Conference on Lung Cancer.
The AZD9291 Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (AURA3) trial enrolled 419 patients at 126 international sites during 2014 and 2015. The trial’s primary endpoint was investigator-assessed progression-free survival, which occurred after a median of 10.1 months with osimertinib and 4.4 months with standard chemotherapy, a statistically significant 70% relative risk reduction (P less than .001) in the hazard for death or progressive disease. The drug was as effective for patients with central nervous system metastases as it was for the other patients, which Dr. Papadimitrakopoulou attributed to osimertinib’s good penetration across the blood-brain barrier. The drug’s overall performance in AURA3 was completely consistent with the results of earlier studies that led to its U.S. approval.
Despite that approval, routine testing for T790M mutations and routine prescribing of osimertinib to positive patients “has not fully penetrated U.S. practice,” Dr. Papadimitrakopoulou said, but she hoped that these new confirmatory data will now firmly establish it as standard of care for the tested population.
Osimertinib is now under testing as first-line TKI treatment for EGFR-positive NSCLC regardless of the tumor’s T790M status. It’s going head to head with two first-generation EGFR TKIs, gefitinib and erlotinib, in the FLAURA trial, which should have reportable results in 2017. “We are very encouraged by the AURA3 data that osimertinib could beat the first-generation TKIs” for first-line treatment, she said.
AURA3 was sponsored by AstraZeneca, which markets osimertinib (Tagrisso). Dr. Papadimitrakopoulou is a consultant to, and has received research support from, AstraZeneca and several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
VIENNA – Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor that received U.S. marketing approval in November 2015 as second-line treatment for selected patients with non–small-cell lung cancer based on phase II trial data, now has the pivotal-trial results that completely justify that action.
During a median follow-up of just over 8 months, patients who had progressed on their first-line EGFR tyrosine kinase inhibitor (TKI) and carried the T790M mutation and switched to osimertinib (Tagrisso) had “overwhelmingly” better response rates and progression-free survival, compared with patients put on standard-of-care chemotherapy in a multicenter randomized trial involving 419 patients, Vassiliki A. Papadimitrakopoulou, MD, reported at the World Conference on Lung Cancer.
The AZD9291 Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (AURA3) trial enrolled 419 patients at 126 international sites during 2014 and 2015. The trial’s primary endpoint was investigator-assessed progression-free survival, which occurred after a median of 10.1 months with osimertinib and 4.4 months with standard chemotherapy, a statistically significant 70% relative risk reduction (P less than .001) in the hazard for death or progressive disease. The drug was as effective for patients with central nervous system metastases as it was for the other patients, which Dr. Papadimitrakopoulou attributed to osimertinib’s good penetration across the blood-brain barrier. The drug’s overall performance in AURA3 was completely consistent with the results of earlier studies that led to its U.S. approval.
Despite that approval, routine testing for T790M mutations and routine prescribing of osimertinib to positive patients “has not fully penetrated U.S. practice,” Dr. Papadimitrakopoulou said, but she hoped that these new confirmatory data will now firmly establish it as standard of care for the tested population.
Osimertinib is now under testing as first-line TKI treatment for EGFR-positive NSCLC regardless of the tumor’s T790M status. It’s going head to head with two first-generation EGFR TKIs, gefitinib and erlotinib, in the FLAURA trial, which should have reportable results in 2017. “We are very encouraged by the AURA3 data that osimertinib could beat the first-generation TKIs” for first-line treatment, she said.
AURA3 was sponsored by AstraZeneca, which markets osimertinib (Tagrisso). Dr. Papadimitrakopoulou is a consultant to, and has received research support from, AstraZeneca and several other companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
Key clinical point:
Major finding: Progression-free survival averaged 10.1 months with osimertinib and 4.4 months in patients on standard chemotherapy.
Data source: AURA3, which randomized 419 patients at 126 international centers.
Disclosures: AURA3 was sponsored by AstraZeneca, which markets osimertinib (Tagrisso). Dr. Papadimitrakopoulou is a consultant to, and has received research support from, AstraZeneca and several other companies.
‘Vanishing’ role forecast for whole-brain irradiation for NSCLC metastases
VIENNA – Icotinib proved significantly more effective and less toxic than standard therapy with whole-brain irradiation and chemotherapy in patients with multiple brain metastases from epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer in the phase III BRAIN trial.
“With favorable objective response and disease control rates, icotinib was superior to whole-brain irradiation with chemotherapy, and therefore icotinib should be used as first-line therapy for advanced EGFR-mutant non–small cell lung cancers with brain metastases,” Yi-long Wu, MD, said in presenting the BRAIN results at the World Congress on Lung Cancer.
Patients with brain metastases are often excluded from participation in clinical trials because their prognosis is so poor. BRAIN is the first phase III trial to report results comparing an EGFR tyrosine kinase inhibitor (TKI) – icotinib – to whole-brain irradiation (WBI) plus chemotherapy, regarded in National Comprehensive Cancer Network guidelines as standard therapy in the setting of brain metastases from NSCLC, noted Dr. Wu of the Guangdong Lung Cancer Institute in Guangzhou, China.
BRAIN was a multicenter Chinese trial in which investigators randomized 158 patients with three or more brain metastases from EGFR-mutated NSCLC to oral icotinib at 125 mg t.i.d. or to WBI with four to six cycles of concurrent or sequential platinum-based chemotherapy.
Icotinib outperformed standard therapy with WBI plus chemotherapy on multiple efficacy endpoints. Median intracranial progression-free survival was 10 months with icotinib, compared with only 4.8 months in patients on WBI with chemotherapy. At 6 months, 72% of patients assigned to icotinib remained free of intracranial disease progression, compared with just 48% of controls on WBI and chemotherapy. Six-month overall PFS, intracranial as well as extracranial, was 6.8 months with icotinib and 3.4 months in the WBI group. The intracranial and overall objective response rates were 67% and 55%, respectively, with icotinib, compared with 41% and 11% with WBI.
In addition, the EGFR TKI had a significantly better safety profile: grade 3 or worse toxicities occurred in just 8% of the icotinib group, compared with 26% of controls on standard therapy, Dr. Wu reported at the meeting sponsored by the International Association for the Study of Lung Cancer.
There was, however, no significant difference between the two study arms in overall survival: 18 months with icotinib, 20.5 months with standard therapy, noted Dr. Wu, who is president of the Chinese Society of Clinical Oncology.
Discussant Jacek Jassem, MD, said “This is potentially, and likely, a practice-changing study.” He added that he’s looking forward to planned future presentation of neurotoxicity and quality of life data from BRAIN. Those important endpoints are also incorporated in the ongoing phase III trials of gefitinib and erlotinib, EGFR TKIs which are far more readily accessible at present to physicians outside the Far East.
“Whole-brain radiotherapy for brain metastases from EGFR-mutated non–small cell lung cancer is a vanishing approach. The remaining role in this setting is as salvage in cases of symptomatic primary or secondary resistance to EGFR TKIs,” said Dr. Jassem, head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.
By way of background, he noted that 10%-15% of patients already have brain metastases at the time of diagnosis of NSCLC, and 40% develop them eventually. EGFR-mutated primary tumors are particularly likely to metastasize to the brain.
Remaining questions in the wake of the BRAIN trial include the efficacy of gefitinib and erlotinib versus WBI plus chemotherapy, as well as the broader question of the efficacy of EGFR TKIs in non-Asian patients with brain metastases.
“Most of the studies of EGFR TKIs have been in East Asian populations. These agents are particularly active in East Asians. There’s a question as to whether the BRAIN results can be applied to other populations,” Dr. Jassem said.
The BRAIN study was sponsored by the Guangdong Association of Clinical Trials. Dr. Wu reported serving as a consultant to AstraZeneca, Roche, Eli Lilly, Pfizer, and Sanofi. Dr. Jassem reported having no financial conflicts of interest.
VIENNA – Icotinib proved significantly more effective and less toxic than standard therapy with whole-brain irradiation and chemotherapy in patients with multiple brain metastases from epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer in the phase III BRAIN trial.
“With favorable objective response and disease control rates, icotinib was superior to whole-brain irradiation with chemotherapy, and therefore icotinib should be used as first-line therapy for advanced EGFR-mutant non–small cell lung cancers with brain metastases,” Yi-long Wu, MD, said in presenting the BRAIN results at the World Congress on Lung Cancer.
Patients with brain metastases are often excluded from participation in clinical trials because their prognosis is so poor. BRAIN is the first phase III trial to report results comparing an EGFR tyrosine kinase inhibitor (TKI) – icotinib – to whole-brain irradiation (WBI) plus chemotherapy, regarded in National Comprehensive Cancer Network guidelines as standard therapy in the setting of brain metastases from NSCLC, noted Dr. Wu of the Guangdong Lung Cancer Institute in Guangzhou, China.
BRAIN was a multicenter Chinese trial in which investigators randomized 158 patients with three or more brain metastases from EGFR-mutated NSCLC to oral icotinib at 125 mg t.i.d. or to WBI with four to six cycles of concurrent or sequential platinum-based chemotherapy.
Icotinib outperformed standard therapy with WBI plus chemotherapy on multiple efficacy endpoints. Median intracranial progression-free survival was 10 months with icotinib, compared with only 4.8 months in patients on WBI with chemotherapy. At 6 months, 72% of patients assigned to icotinib remained free of intracranial disease progression, compared with just 48% of controls on WBI and chemotherapy. Six-month overall PFS, intracranial as well as extracranial, was 6.8 months with icotinib and 3.4 months in the WBI group. The intracranial and overall objective response rates were 67% and 55%, respectively, with icotinib, compared with 41% and 11% with WBI.
In addition, the EGFR TKI had a significantly better safety profile: grade 3 or worse toxicities occurred in just 8% of the icotinib group, compared with 26% of controls on standard therapy, Dr. Wu reported at the meeting sponsored by the International Association for the Study of Lung Cancer.
There was, however, no significant difference between the two study arms in overall survival: 18 months with icotinib, 20.5 months with standard therapy, noted Dr. Wu, who is president of the Chinese Society of Clinical Oncology.
Discussant Jacek Jassem, MD, said “This is potentially, and likely, a practice-changing study.” He added that he’s looking forward to planned future presentation of neurotoxicity and quality of life data from BRAIN. Those important endpoints are also incorporated in the ongoing phase III trials of gefitinib and erlotinib, EGFR TKIs which are far more readily accessible at present to physicians outside the Far East.
“Whole-brain radiotherapy for brain metastases from EGFR-mutated non–small cell lung cancer is a vanishing approach. The remaining role in this setting is as salvage in cases of symptomatic primary or secondary resistance to EGFR TKIs,” said Dr. Jassem, head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.
By way of background, he noted that 10%-15% of patients already have brain metastases at the time of diagnosis of NSCLC, and 40% develop them eventually. EGFR-mutated primary tumors are particularly likely to metastasize to the brain.
Remaining questions in the wake of the BRAIN trial include the efficacy of gefitinib and erlotinib versus WBI plus chemotherapy, as well as the broader question of the efficacy of EGFR TKIs in non-Asian patients with brain metastases.
“Most of the studies of EGFR TKIs have been in East Asian populations. These agents are particularly active in East Asians. There’s a question as to whether the BRAIN results can be applied to other populations,” Dr. Jassem said.
The BRAIN study was sponsored by the Guangdong Association of Clinical Trials. Dr. Wu reported serving as a consultant to AstraZeneca, Roche, Eli Lilly, Pfizer, and Sanofi. Dr. Jassem reported having no financial conflicts of interest.
VIENNA – Icotinib proved significantly more effective and less toxic than standard therapy with whole-brain irradiation and chemotherapy in patients with multiple brain metastases from epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer in the phase III BRAIN trial.
“With favorable objective response and disease control rates, icotinib was superior to whole-brain irradiation with chemotherapy, and therefore icotinib should be used as first-line therapy for advanced EGFR-mutant non–small cell lung cancers with brain metastases,” Yi-long Wu, MD, said in presenting the BRAIN results at the World Congress on Lung Cancer.
Patients with brain metastases are often excluded from participation in clinical trials because their prognosis is so poor. BRAIN is the first phase III trial to report results comparing an EGFR tyrosine kinase inhibitor (TKI) – icotinib – to whole-brain irradiation (WBI) plus chemotherapy, regarded in National Comprehensive Cancer Network guidelines as standard therapy in the setting of brain metastases from NSCLC, noted Dr. Wu of the Guangdong Lung Cancer Institute in Guangzhou, China.
BRAIN was a multicenter Chinese trial in which investigators randomized 158 patients with three or more brain metastases from EGFR-mutated NSCLC to oral icotinib at 125 mg t.i.d. or to WBI with four to six cycles of concurrent or sequential platinum-based chemotherapy.
Icotinib outperformed standard therapy with WBI plus chemotherapy on multiple efficacy endpoints. Median intracranial progression-free survival was 10 months with icotinib, compared with only 4.8 months in patients on WBI with chemotherapy. At 6 months, 72% of patients assigned to icotinib remained free of intracranial disease progression, compared with just 48% of controls on WBI and chemotherapy. Six-month overall PFS, intracranial as well as extracranial, was 6.8 months with icotinib and 3.4 months in the WBI group. The intracranial and overall objective response rates were 67% and 55%, respectively, with icotinib, compared with 41% and 11% with WBI.
In addition, the EGFR TKI had a significantly better safety profile: grade 3 or worse toxicities occurred in just 8% of the icotinib group, compared with 26% of controls on standard therapy, Dr. Wu reported at the meeting sponsored by the International Association for the Study of Lung Cancer.
There was, however, no significant difference between the two study arms in overall survival: 18 months with icotinib, 20.5 months with standard therapy, noted Dr. Wu, who is president of the Chinese Society of Clinical Oncology.
Discussant Jacek Jassem, MD, said “This is potentially, and likely, a practice-changing study.” He added that he’s looking forward to planned future presentation of neurotoxicity and quality of life data from BRAIN. Those important endpoints are also incorporated in the ongoing phase III trials of gefitinib and erlotinib, EGFR TKIs which are far more readily accessible at present to physicians outside the Far East.
“Whole-brain radiotherapy for brain metastases from EGFR-mutated non–small cell lung cancer is a vanishing approach. The remaining role in this setting is as salvage in cases of symptomatic primary or secondary resistance to EGFR TKIs,” said Dr. Jassem, head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.
By way of background, he noted that 10%-15% of patients already have brain metastases at the time of diagnosis of NSCLC, and 40% develop them eventually. EGFR-mutated primary tumors are particularly likely to metastasize to the brain.
Remaining questions in the wake of the BRAIN trial include the efficacy of gefitinib and erlotinib versus WBI plus chemotherapy, as well as the broader question of the efficacy of EGFR TKIs in non-Asian patients with brain metastases.
“Most of the studies of EGFR TKIs have been in East Asian populations. These agents are particularly active in East Asians. There’s a question as to whether the BRAIN results can be applied to other populations,” Dr. Jassem said.
The BRAIN study was sponsored by the Guangdong Association of Clinical Trials. Dr. Wu reported serving as a consultant to AstraZeneca, Roche, Eli Lilly, Pfizer, and Sanofi. Dr. Jassem reported having no financial conflicts of interest.
AT WCLC 2016
Key clinical point:
Major finding: Median intracranial progression-free survival in patients with multiple brain metastases from EGFR-mutated NSCLC was 10 months in those randomized to icotinib, compared with 4.8 months with standard-of-care whole-brain irradiation plus chemotherapy.
Data source: This phase III multicenter Chinese trial included 158 patients with multiple brain metastases from EGFR-mutated NSCLC.
Disclosures: The BRAIN study was sponsored by the Guangdong Association of Clinical Trials. The presenter reported serving as a consultant to AstraZeneca, Roche, Eli Lilly, Pfizer, and Sanofi.
Ganetespib fails to hit mark in phase III NSCLC trial
VIENNA – The addition of ganetespib to docetaxel for the treatment of advanced non–small cell lung cancer (NSCLC) did not live up to its earlier promise of improved efficacy over docetaxel alone in a phase III study.
Interim results of the GALAXY-2 study, which led to the trial’s termination for futility, showed that there was no difference in the primary endpoint of overall survival (OS). The median OS was a respective 10.9 months and 10.5 months for the combination of ganetespib plus docetaxel versus docetaxel alone (hazard ratio, 1.111, 95% confidence interval, 0.899-1.372, P = .03293).
The combination had looked promising in the phase II GALAXY-1 study (Ann Oncol. 2015;26:1741-8), with a trend towards improved PFS and OS, with patients diagnosed with advanced disease perhaps gaining the most benefit.
“The addition of ganetespib to docetaxel did not result in improved efficacy for the salvage therapy of patients with advanced-stage lung adenocarcinoma,” Rathi Pillai, MD, said at the World Conference on Lung Cancer.
“Based on these findings, further development of Hsp [heat shock protein] 90 inhibitors in lung cancer should be limited to patients with driver mutations with relevant client proteins,” added Dr. Pillai of the Winship Cancer Institute at Emory University in Atlanta.
In GALAXY-2, 672 patients were randomized, 1:1, to receive docetaxel (75 mg/m2 on day 1) with ganetespib (150 mg/m2 on days 1 and 15) or a placebo every 3 weeks. The median number of cycles received was five in the combination arm and four in the docetaxel-only arm. All patients had advanced non–small cell lung adenocarcinoma diagnosed at least 6 months prior to enrollment and had received only one prior treatment regimen.
Response rates were similar between the two groups, with 13.7% and 16% of ganetespib/docetaxel– and docetaxel/placebo–treated patients achieving a partial response (P = .448) and 56.1% and 50.1%, respectively, having stable disease (P = .123).
Almost two-thirds (65%) of patients given ganetespib/docetaxel reported any grade 3-4 adverse event versus 54% of patients given docetaxel/placebo. The most frequent treatment-emergent grade 3-4 adverse event was neutropenia, occurring in 34.6% ad 29.5% of patients in each arm (P = .1807), with only diarrhea (46.2% vs. 14.6%; P less than .0001) and weight loss (11.3% vs. 5.2%; P = .0044) occurring more frequently in the combination than the docetaxel-only arm.
Ganetespib is a second-generation Hsp90 inhibitor and the rationale for using Hsp90 inhibitors as cancer therapy remains sound, Dr. Gandara maintained. One of the issues is finding a biomarker to predict the benefit for these drugs in a clinical setting, he said. In the phase II GALAXY-1 trial it was noted that patients diagnosed with advanced disease more than 6 months prior to study entry fared better than those with more recent diagnosis if they were treated with ganetespib/docetaxel than docetaxel alone. Patients with elevated levels of lactate dehydrogenase (eLDH) also seemed to do better than those with normal LDH levels if they were treated with the combination.
These two subpopulations were specifically looked at the in the phase III study, but again no differences in OS or PFS were observed, nor were differences observed in any of the other subgroups analyzed, which included EGFR- and ALK-negative patients, by response rate or progression because of new metastatic lesions.
“Were these the right surrogates to use as predictive biomarkers for heat shock protein inhibition? Of course, in retrospect, it is easy to say that they were not,” Dr. Gandara said.
“Is there still an opportunity for this class of drugs to make a meaningful impact in NSCLC? In my own opinion I think the answer is yes, but not in this broad page approach and not with these potential surrogates as were used in GALAXY-2,” he said at the meeting sponsored by the International Association for the Study of Lung Cancer.
The study was sponsored by Synta Pharmaceuticals, which became part of Madrigal Pharmaceuticals in June 2016. Dr. Pillai reported having no financial disclosures. Dr. Gandara disclosed that he had received research grants from several pharmaceutical companies.
VIENNA – The addition of ganetespib to docetaxel for the treatment of advanced non–small cell lung cancer (NSCLC) did not live up to its earlier promise of improved efficacy over docetaxel alone in a phase III study.
Interim results of the GALAXY-2 study, which led to the trial’s termination for futility, showed that there was no difference in the primary endpoint of overall survival (OS). The median OS was a respective 10.9 months and 10.5 months for the combination of ganetespib plus docetaxel versus docetaxel alone (hazard ratio, 1.111, 95% confidence interval, 0.899-1.372, P = .03293).
The combination had looked promising in the phase II GALAXY-1 study (Ann Oncol. 2015;26:1741-8), with a trend towards improved PFS and OS, with patients diagnosed with advanced disease perhaps gaining the most benefit.
“The addition of ganetespib to docetaxel did not result in improved efficacy for the salvage therapy of patients with advanced-stage lung adenocarcinoma,” Rathi Pillai, MD, said at the World Conference on Lung Cancer.
“Based on these findings, further development of Hsp [heat shock protein] 90 inhibitors in lung cancer should be limited to patients with driver mutations with relevant client proteins,” added Dr. Pillai of the Winship Cancer Institute at Emory University in Atlanta.
In GALAXY-2, 672 patients were randomized, 1:1, to receive docetaxel (75 mg/m2 on day 1) with ganetespib (150 mg/m2 on days 1 and 15) or a placebo every 3 weeks. The median number of cycles received was five in the combination arm and four in the docetaxel-only arm. All patients had advanced non–small cell lung adenocarcinoma diagnosed at least 6 months prior to enrollment and had received only one prior treatment regimen.
Response rates were similar between the two groups, with 13.7% and 16% of ganetespib/docetaxel– and docetaxel/placebo–treated patients achieving a partial response (P = .448) and 56.1% and 50.1%, respectively, having stable disease (P = .123).
Almost two-thirds (65%) of patients given ganetespib/docetaxel reported any grade 3-4 adverse event versus 54% of patients given docetaxel/placebo. The most frequent treatment-emergent grade 3-4 adverse event was neutropenia, occurring in 34.6% ad 29.5% of patients in each arm (P = .1807), with only diarrhea (46.2% vs. 14.6%; P less than .0001) and weight loss (11.3% vs. 5.2%; P = .0044) occurring more frequently in the combination than the docetaxel-only arm.
Ganetespib is a second-generation Hsp90 inhibitor and the rationale for using Hsp90 inhibitors as cancer therapy remains sound, Dr. Gandara maintained. One of the issues is finding a biomarker to predict the benefit for these drugs in a clinical setting, he said. In the phase II GALAXY-1 trial it was noted that patients diagnosed with advanced disease more than 6 months prior to study entry fared better than those with more recent diagnosis if they were treated with ganetespib/docetaxel than docetaxel alone. Patients with elevated levels of lactate dehydrogenase (eLDH) also seemed to do better than those with normal LDH levels if they were treated with the combination.
These two subpopulations were specifically looked at the in the phase III study, but again no differences in OS or PFS were observed, nor were differences observed in any of the other subgroups analyzed, which included EGFR- and ALK-negative patients, by response rate or progression because of new metastatic lesions.
“Were these the right surrogates to use as predictive biomarkers for heat shock protein inhibition? Of course, in retrospect, it is easy to say that they were not,” Dr. Gandara said.
“Is there still an opportunity for this class of drugs to make a meaningful impact in NSCLC? In my own opinion I think the answer is yes, but not in this broad page approach and not with these potential surrogates as were used in GALAXY-2,” he said at the meeting sponsored by the International Association for the Study of Lung Cancer.
The study was sponsored by Synta Pharmaceuticals, which became part of Madrigal Pharmaceuticals in June 2016. Dr. Pillai reported having no financial disclosures. Dr. Gandara disclosed that he had received research grants from several pharmaceutical companies.
VIENNA – The addition of ganetespib to docetaxel for the treatment of advanced non–small cell lung cancer (NSCLC) did not live up to its earlier promise of improved efficacy over docetaxel alone in a phase III study.
Interim results of the GALAXY-2 study, which led to the trial’s termination for futility, showed that there was no difference in the primary endpoint of overall survival (OS). The median OS was a respective 10.9 months and 10.5 months for the combination of ganetespib plus docetaxel versus docetaxel alone (hazard ratio, 1.111, 95% confidence interval, 0.899-1.372, P = .03293).
The combination had looked promising in the phase II GALAXY-1 study (Ann Oncol. 2015;26:1741-8), with a trend towards improved PFS and OS, with patients diagnosed with advanced disease perhaps gaining the most benefit.
“The addition of ganetespib to docetaxel did not result in improved efficacy for the salvage therapy of patients with advanced-stage lung adenocarcinoma,” Rathi Pillai, MD, said at the World Conference on Lung Cancer.
“Based on these findings, further development of Hsp [heat shock protein] 90 inhibitors in lung cancer should be limited to patients with driver mutations with relevant client proteins,” added Dr. Pillai of the Winship Cancer Institute at Emory University in Atlanta.
In GALAXY-2, 672 patients were randomized, 1:1, to receive docetaxel (75 mg/m2 on day 1) with ganetespib (150 mg/m2 on days 1 and 15) or a placebo every 3 weeks. The median number of cycles received was five in the combination arm and four in the docetaxel-only arm. All patients had advanced non–small cell lung adenocarcinoma diagnosed at least 6 months prior to enrollment and had received only one prior treatment regimen.
Response rates were similar between the two groups, with 13.7% and 16% of ganetespib/docetaxel– and docetaxel/placebo–treated patients achieving a partial response (P = .448) and 56.1% and 50.1%, respectively, having stable disease (P = .123).
Almost two-thirds (65%) of patients given ganetespib/docetaxel reported any grade 3-4 adverse event versus 54% of patients given docetaxel/placebo. The most frequent treatment-emergent grade 3-4 adverse event was neutropenia, occurring in 34.6% ad 29.5% of patients in each arm (P = .1807), with only diarrhea (46.2% vs. 14.6%; P less than .0001) and weight loss (11.3% vs. 5.2%; P = .0044) occurring more frequently in the combination than the docetaxel-only arm.
Ganetespib is a second-generation Hsp90 inhibitor and the rationale for using Hsp90 inhibitors as cancer therapy remains sound, Dr. Gandara maintained. One of the issues is finding a biomarker to predict the benefit for these drugs in a clinical setting, he said. In the phase II GALAXY-1 trial it was noted that patients diagnosed with advanced disease more than 6 months prior to study entry fared better than those with more recent diagnosis if they were treated with ganetespib/docetaxel than docetaxel alone. Patients with elevated levels of lactate dehydrogenase (eLDH) also seemed to do better than those with normal LDH levels if they were treated with the combination.
These two subpopulations were specifically looked at the in the phase III study, but again no differences in OS or PFS were observed, nor were differences observed in any of the other subgroups analyzed, which included EGFR- and ALK-negative patients, by response rate or progression because of new metastatic lesions.
“Were these the right surrogates to use as predictive biomarkers for heat shock protein inhibition? Of course, in retrospect, it is easy to say that they were not,” Dr. Gandara said.
“Is there still an opportunity for this class of drugs to make a meaningful impact in NSCLC? In my own opinion I think the answer is yes, but not in this broad page approach and not with these potential surrogates as were used in GALAXY-2,” he said at the meeting sponsored by the International Association for the Study of Lung Cancer.
The study was sponsored by Synta Pharmaceuticals, which became part of Madrigal Pharmaceuticals in June 2016. Dr. Pillai reported having no financial disclosures. Dr. Gandara disclosed that he had received research grants from several pharmaceutical companies.
AT WCLC 2016
Key clinical point: Adding ganetespib to docetaxel did not improve the survival of the patients studied versus docetaxel alone.
Major finding: Median overall survival was 10.9 months for ganetespib/docetaxel and 10.5 months for docetaxel alone (HR, 1.111; 95% CI, 0.899-1.372; P = .03293).
Data source: International, randomized, phase III, open-label GALAXY-2 study of docetaxel with or without ganetespib in 672 patients with advanced non–small cell lung adenocarcinoma.
Disclosures: The study was sponsored by Synta Pharmaceuticals (Madrigal Pharmaceuticals since June 2016). Dr. Pillai reported having no financial disclosures. Dr. Gandara disclosed that he had received research grants from several pharmaceutical companies.
VIDEO: Checkpoint inhibitors show few efficacy, safety differences
VIENNA – The two subclasses of immune checkpoint inhibitor drugs showed very little basis for choosing between them by either efficacy or toxicity in a systematic review of 23 trials run in patients with non–small cell lung cancer during 2013-2016.
For efficacy, inhibitors of the programmed death (PD-1) receptors had a 19% overall response rate when averaged from 12 different trials with 3,284 patients on one of these drugs. The PD-ligand 1 (PD-L1) inhibitors produced a 17% overall response rate in 11 trials with 2,615 patients on one of the drugs, a between-class efficacy difference that was not statistically significant, Rathi N. Pillai, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
Immune-related adverse events were significantly more common in the patients treated with PD-1 inhibitors: 16%, compared with 11% in the PD-L1 inhibitor-treated patients (P = .04). The two subclasses also showed a trend toward a difference in the most common immune-related adverse event, hypothyroidism, with an incidence of 6.7% with PD-1 inhibitors and 4.2% with PD-L1 inhibitors (P = .07). The two sets of patients showed a statistically significant difference in the next most common immune-related adverse event, pneunomitis, 4.0% with PD-1 inhibitors and 2.0% with PD-L1 inhibitors (P = .02).
The trials with PD-1 inhibitors included nivolumab (Opdivo) and pembrolizumab (Keytruda). The trials with PD-L1 inhibitors included atezolizumab (Tecentriq), durvalumab, and avelumab. The total rate of all adverse events was highest among patients on nivolumab, 76%, and lowest among patients on durvalumab, 61%.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
This very important systematic review with data from a total of nearly 6,000 patients shows that severe toxicity is unusual with the PD-1 and PD-L1 inhibitors, and they result in no meaningful difference in response rates. The toxicities seen with these drugs are milder and less frequent than we see with standard chemotherapy drugs. The severe autoimmune toxicities seen are a major concern but are manageable and occurred at low rates.
In general, efficacy and toxicity does not appear to form a basis by which to choose among these drugs. Fatigue was the most common adverse event, which is surprising to see with these drugs although we are accustomed to seeing it in patients on standard chemotherapy. Fatigue can be a major issue for patients, even if it is relatively mild, because they remain on these drugs for periods as long as 2 years.
If the PD-1 and PD-L1 inhibitors continue to perform with similar efficacy and safety profiles, clinicians will be forced to turn to other parameters when trying to decide which drug specifically to prescribe. This can include issues of cost, reimbursement, and dosing convenience. Nivolumab, for example, has been administered more often, every 2 weeks, than the other drugs in these classes. Oncologists are trying to develop effective regimens with these drugs that can be given once every 3 or every 4 weeks. Future investigations may also look at the possibility of treating patients with these drugs initially for 6 months, and then scaling back to retreatment only when there is disease progression. If this approach is successful, it would obviate concerns about causing long-term fatigue or the inconvenience of more frequent treatment schedules.
We also need to continue to monitor and compare the toxicities of these immune checkpoint inhibitors as we move into using them in combination regimens.
Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Merck/MSD, Merck Serono, and Roche, and he has received honoraria from Merck and Roche, and he has received travel grants from BMS and Roche. He made these comments as the designated discussant for the report and in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
This very important systematic review with data from a total of nearly 6,000 patients shows that severe toxicity is unusual with the PD-1 and PD-L1 inhibitors, and they result in no meaningful difference in response rates. The toxicities seen with these drugs are milder and less frequent than we see with standard chemotherapy drugs. The severe autoimmune toxicities seen are a major concern but are manageable and occurred at low rates.
In general, efficacy and toxicity does not appear to form a basis by which to choose among these drugs. Fatigue was the most common adverse event, which is surprising to see with these drugs although we are accustomed to seeing it in patients on standard chemotherapy. Fatigue can be a major issue for patients, even if it is relatively mild, because they remain on these drugs for periods as long as 2 years.
If the PD-1 and PD-L1 inhibitors continue to perform with similar efficacy and safety profiles, clinicians will be forced to turn to other parameters when trying to decide which drug specifically to prescribe. This can include issues of cost, reimbursement, and dosing convenience. Nivolumab, for example, has been administered more often, every 2 weeks, than the other drugs in these classes. Oncologists are trying to develop effective regimens with these drugs that can be given once every 3 or every 4 weeks. Future investigations may also look at the possibility of treating patients with these drugs initially for 6 months, and then scaling back to retreatment only when there is disease progression. If this approach is successful, it would obviate concerns about causing long-term fatigue or the inconvenience of more frequent treatment schedules.
We also need to continue to monitor and compare the toxicities of these immune checkpoint inhibitors as we move into using them in combination regimens.
Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Merck/MSD, Merck Serono, and Roche, and he has received honoraria from Merck and Roche, and he has received travel grants from BMS and Roche. He made these comments as the designated discussant for the report and in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
This very important systematic review with data from a total of nearly 6,000 patients shows that severe toxicity is unusual with the PD-1 and PD-L1 inhibitors, and they result in no meaningful difference in response rates. The toxicities seen with these drugs are milder and less frequent than we see with standard chemotherapy drugs. The severe autoimmune toxicities seen are a major concern but are manageable and occurred at low rates.
In general, efficacy and toxicity does not appear to form a basis by which to choose among these drugs. Fatigue was the most common adverse event, which is surprising to see with these drugs although we are accustomed to seeing it in patients on standard chemotherapy. Fatigue can be a major issue for patients, even if it is relatively mild, because they remain on these drugs for periods as long as 2 years.
If the PD-1 and PD-L1 inhibitors continue to perform with similar efficacy and safety profiles, clinicians will be forced to turn to other parameters when trying to decide which drug specifically to prescribe. This can include issues of cost, reimbursement, and dosing convenience. Nivolumab, for example, has been administered more often, every 2 weeks, than the other drugs in these classes. Oncologists are trying to develop effective regimens with these drugs that can be given once every 3 or every 4 weeks. Future investigations may also look at the possibility of treating patients with these drugs initially for 6 months, and then scaling back to retreatment only when there is disease progression. If this approach is successful, it would obviate concerns about causing long-term fatigue or the inconvenience of more frequent treatment schedules.
We also need to continue to monitor and compare the toxicities of these immune checkpoint inhibitors as we move into using them in combination regimens.
Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Merck/MSD, Merck Serono, and Roche, and he has received honoraria from Merck and Roche, and he has received travel grants from BMS and Roche. He made these comments as the designated discussant for the report and in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
VIENNA – The two subclasses of immune checkpoint inhibitor drugs showed very little basis for choosing between them by either efficacy or toxicity in a systematic review of 23 trials run in patients with non–small cell lung cancer during 2013-2016.
For efficacy, inhibitors of the programmed death (PD-1) receptors had a 19% overall response rate when averaged from 12 different trials with 3,284 patients on one of these drugs. The PD-ligand 1 (PD-L1) inhibitors produced a 17% overall response rate in 11 trials with 2,615 patients on one of the drugs, a between-class efficacy difference that was not statistically significant, Rathi N. Pillai, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
Immune-related adverse events were significantly more common in the patients treated with PD-1 inhibitors: 16%, compared with 11% in the PD-L1 inhibitor-treated patients (P = .04). The two subclasses also showed a trend toward a difference in the most common immune-related adverse event, hypothyroidism, with an incidence of 6.7% with PD-1 inhibitors and 4.2% with PD-L1 inhibitors (P = .07). The two sets of patients showed a statistically significant difference in the next most common immune-related adverse event, pneunomitis, 4.0% with PD-1 inhibitors and 2.0% with PD-L1 inhibitors (P = .02).
The trials with PD-1 inhibitors included nivolumab (Opdivo) and pembrolizumab (Keytruda). The trials with PD-L1 inhibitors included atezolizumab (Tecentriq), durvalumab, and avelumab. The total rate of all adverse events was highest among patients on nivolumab, 76%, and lowest among patients on durvalumab, 61%.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
VIENNA – The two subclasses of immune checkpoint inhibitor drugs showed very little basis for choosing between them by either efficacy or toxicity in a systematic review of 23 trials run in patients with non–small cell lung cancer during 2013-2016.
For efficacy, inhibitors of the programmed death (PD-1) receptors had a 19% overall response rate when averaged from 12 different trials with 3,284 patients on one of these drugs. The PD-ligand 1 (PD-L1) inhibitors produced a 17% overall response rate in 11 trials with 2,615 patients on one of the drugs, a between-class efficacy difference that was not statistically significant, Rathi N. Pillai, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
Immune-related adverse events were significantly more common in the patients treated with PD-1 inhibitors: 16%, compared with 11% in the PD-L1 inhibitor-treated patients (P = .04). The two subclasses also showed a trend toward a difference in the most common immune-related adverse event, hypothyroidism, with an incidence of 6.7% with PD-1 inhibitors and 4.2% with PD-L1 inhibitors (P = .07). The two sets of patients showed a statistically significant difference in the next most common immune-related adverse event, pneunomitis, 4.0% with PD-1 inhibitors and 2.0% with PD-L1 inhibitors (P = .02).
The trials with PD-1 inhibitors included nivolumab (Opdivo) and pembrolizumab (Keytruda). The trials with PD-L1 inhibitors included atezolizumab (Tecentriq), durvalumab, and avelumab. The total rate of all adverse events was highest among patients on nivolumab, 76%, and lowest among patients on durvalumab, 61%.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT WCLC 2016
Key clinical point:
Major finding: Overall response rates were 19% using a PD-1 inhibitor and 17% when using a PD-L1 inhibitor.
Data source: A systematic review of 23 trials in patients with non–small cell lung cancer published during 2013-2016.
Disclosures: Dr. Pillai had no disclosures.
Nivolumab plus ipilimumab shines as first-line in advanced NSCLC
VIENNA – The combination of nivolumab and ipilimumab as first-line therapy in patients with advanced non–small cell lung cancer (NSCLC) doubled median progression-free survival time compared with nivolumab monotherapy in updated results from the CheckMate 012 trial, Scott N. Gettinger, MD, reported at the World Congress on Lung Cancer.
This doubling of progression-free survival (PFS) applied to all comers regardless of whether or not their tumor expressed programmed death-ligand 1 (PD-L1). In those patients with any degree of PD-L1 expression – even if just 1% of tumor cells stained positive – combination therapy didn’t just double median PFS, it tripled it, compared with nivolumab alone, added Dr. Gettinger of the Yale Cancer Center in New Haven, Conn.
CheckMate 012 is a phase I study of nivolumab as first-line therapy for advanced NSCLC with numerous treatment arms. Dr. Gettinger presented updated results for 52 patients who received intravenous nivolumab monotherapy at a dose of 3 mg/kg every 2 weeks, 36 patients on nivolumab plus intravenous ipilimumab at 1 mg/kg every 12 weeks, and 39 who received nivolumab plus ipilimumab every 6 weeks. None of the participants had prior chemotherapy for their advanced stage IIIb or IV NSCLC.
Median PFS in the overall study population was 3.6 months with nivolumab monotherapy and 8.0 months with combination therapy. In the roughly 70% of participants who had any degree of tumor PD-L1 expression, median PFS was 3.5 months with monotherapy, compared with 12.7 months in the combined dual therapy arms. And, in the roughly one-quarter of patients whose tumor showed at least 50% PD-L1 expression, median PFS rose to 8.3 months with nivolumab monotherapy and hasn’t yet been reached in patients on combination therapy.
The 1-year overall survival rate in patients on nivolumab monotherapy was 73% in all treated patients, 69% in those with any detectable tumor PD-L1 expression, and 83% in patients with at least 50% PD-L1 expression. In patients on combination therapy, the corresponding figures were higher at 76%, 87%, and 100%.
The clearly enhanced efficacy achieved with the combination of nivolumab plus ipilimumab was accomplished with only a modest increase in toxicity compared with nivolumab alone. At a median follow-up of 22 months in the nivolumab monotherapy group and 16 months for combination therapy, the rate of any treatment-related adverse event leading to study withdrawal was 12% with monotherapy and 18% with combination therapy.
The combination of nivolumab (Opdivo), a PD-L1 immune checkpoint inhibitor, and ipilimumab (Yervoy), a cytotoxic T-lymphocyte–associated protein 4 immune checkpoint inhibitor, is biologically attractive: “The ipilimumab primes the immune system by inducing tumor infiltration of effector T cells while depleting the number of myeloid-derived suppressor cells and suppressive regulatory T cells within the tumor microenvironment,” Dr. Gettinger explained.
Nivolumab is approved for treatment of advanced NSCLC that has progressed despite platinum-based chemotherapy. Of the various toxicities associated with the drug, only dermatologic and GI adverse events occurred more frequently with combination therapy than nivolumab alone.
There were five complete responses in the nivolumab monotherapy group and six with combination therapy. Of note, four of these complete responses occurred in patients without any measurable tumor PD-L1 expression.
Based upon these encouraging results from CheckMate 012, a phase III randomized clinical trial of nivolumab as first-line therapy in patients with advanced NSCLC is underway. In the CheckMate 227 trial, patients with any detectable PD-L1 expression are randomized to nivolumab at 3mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks, nivolumab monotherapy at 240 mg every 2 weeks, or standard platinum-based chemotherapy. Patients with no PD-L1 expression in their tumor are assigned to the nivolumab/ipilimumab combination, or nivolumab at 360 mg every 3 weeks plus chemotherapy, or chemotherapy alone.
“I think we should be cautious despite the excitement about the combination,” argued Dr. Garon, director of thoracic oncology at the University of California, Los Angeles.
He noted that various iterations of the large CheckMate 012 phase I program have been presented repeatedly at major meetings, and the shifting data have raised concerns in his mind about possible patient selection bias stemming from the study design.
“From my perspective, until we see randomized data that can control for these biases, I will remain hopeful but not yet extremely confident that this combination will be the new frontline therapy for metastatic non–small cell lung cancer,” Dr. Garon said.
Dr. Gettinger reported serving as a consultant to Bristol-Myers Squibb, which markets nivolumab.
Dr. Garon reported that his institution receives funding from Bristol-Myers Squibb as well as AstraZeneca, Boehringer Ingelheim, Eli Lilly, Genentech, Mirati, Merck, Pfizer, and Novartis.
VIENNA – The combination of nivolumab and ipilimumab as first-line therapy in patients with advanced non–small cell lung cancer (NSCLC) doubled median progression-free survival time compared with nivolumab monotherapy in updated results from the CheckMate 012 trial, Scott N. Gettinger, MD, reported at the World Congress on Lung Cancer.
This doubling of progression-free survival (PFS) applied to all comers regardless of whether or not their tumor expressed programmed death-ligand 1 (PD-L1). In those patients with any degree of PD-L1 expression – even if just 1% of tumor cells stained positive – combination therapy didn’t just double median PFS, it tripled it, compared with nivolumab alone, added Dr. Gettinger of the Yale Cancer Center in New Haven, Conn.
CheckMate 012 is a phase I study of nivolumab as first-line therapy for advanced NSCLC with numerous treatment arms. Dr. Gettinger presented updated results for 52 patients who received intravenous nivolumab monotherapy at a dose of 3 mg/kg every 2 weeks, 36 patients on nivolumab plus intravenous ipilimumab at 1 mg/kg every 12 weeks, and 39 who received nivolumab plus ipilimumab every 6 weeks. None of the participants had prior chemotherapy for their advanced stage IIIb or IV NSCLC.
Median PFS in the overall study population was 3.6 months with nivolumab monotherapy and 8.0 months with combination therapy. In the roughly 70% of participants who had any degree of tumor PD-L1 expression, median PFS was 3.5 months with monotherapy, compared with 12.7 months in the combined dual therapy arms. And, in the roughly one-quarter of patients whose tumor showed at least 50% PD-L1 expression, median PFS rose to 8.3 months with nivolumab monotherapy and hasn’t yet been reached in patients on combination therapy.
The 1-year overall survival rate in patients on nivolumab monotherapy was 73% in all treated patients, 69% in those with any detectable tumor PD-L1 expression, and 83% in patients with at least 50% PD-L1 expression. In patients on combination therapy, the corresponding figures were higher at 76%, 87%, and 100%.
The clearly enhanced efficacy achieved with the combination of nivolumab plus ipilimumab was accomplished with only a modest increase in toxicity compared with nivolumab alone. At a median follow-up of 22 months in the nivolumab monotherapy group and 16 months for combination therapy, the rate of any treatment-related adverse event leading to study withdrawal was 12% with monotherapy and 18% with combination therapy.
The combination of nivolumab (Opdivo), a PD-L1 immune checkpoint inhibitor, and ipilimumab (Yervoy), a cytotoxic T-lymphocyte–associated protein 4 immune checkpoint inhibitor, is biologically attractive: “The ipilimumab primes the immune system by inducing tumor infiltration of effector T cells while depleting the number of myeloid-derived suppressor cells and suppressive regulatory T cells within the tumor microenvironment,” Dr. Gettinger explained.
Nivolumab is approved for treatment of advanced NSCLC that has progressed despite platinum-based chemotherapy. Of the various toxicities associated with the drug, only dermatologic and GI adverse events occurred more frequently with combination therapy than nivolumab alone.
There were five complete responses in the nivolumab monotherapy group and six with combination therapy. Of note, four of these complete responses occurred in patients without any measurable tumor PD-L1 expression.
Based upon these encouraging results from CheckMate 012, a phase III randomized clinical trial of nivolumab as first-line therapy in patients with advanced NSCLC is underway. In the CheckMate 227 trial, patients with any detectable PD-L1 expression are randomized to nivolumab at 3mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks, nivolumab monotherapy at 240 mg every 2 weeks, or standard platinum-based chemotherapy. Patients with no PD-L1 expression in their tumor are assigned to the nivolumab/ipilimumab combination, or nivolumab at 360 mg every 3 weeks plus chemotherapy, or chemotherapy alone.
“I think we should be cautious despite the excitement about the combination,” argued Dr. Garon, director of thoracic oncology at the University of California, Los Angeles.
He noted that various iterations of the large CheckMate 012 phase I program have been presented repeatedly at major meetings, and the shifting data have raised concerns in his mind about possible patient selection bias stemming from the study design.
“From my perspective, until we see randomized data that can control for these biases, I will remain hopeful but not yet extremely confident that this combination will be the new frontline therapy for metastatic non–small cell lung cancer,” Dr. Garon said.
Dr. Gettinger reported serving as a consultant to Bristol-Myers Squibb, which markets nivolumab.
Dr. Garon reported that his institution receives funding from Bristol-Myers Squibb as well as AstraZeneca, Boehringer Ingelheim, Eli Lilly, Genentech, Mirati, Merck, Pfizer, and Novartis.
VIENNA – The combination of nivolumab and ipilimumab as first-line therapy in patients with advanced non–small cell lung cancer (NSCLC) doubled median progression-free survival time compared with nivolumab monotherapy in updated results from the CheckMate 012 trial, Scott N. Gettinger, MD, reported at the World Congress on Lung Cancer.
This doubling of progression-free survival (PFS) applied to all comers regardless of whether or not their tumor expressed programmed death-ligand 1 (PD-L1). In those patients with any degree of PD-L1 expression – even if just 1% of tumor cells stained positive – combination therapy didn’t just double median PFS, it tripled it, compared with nivolumab alone, added Dr. Gettinger of the Yale Cancer Center in New Haven, Conn.
CheckMate 012 is a phase I study of nivolumab as first-line therapy for advanced NSCLC with numerous treatment arms. Dr. Gettinger presented updated results for 52 patients who received intravenous nivolumab monotherapy at a dose of 3 mg/kg every 2 weeks, 36 patients on nivolumab plus intravenous ipilimumab at 1 mg/kg every 12 weeks, and 39 who received nivolumab plus ipilimumab every 6 weeks. None of the participants had prior chemotherapy for their advanced stage IIIb or IV NSCLC.
Median PFS in the overall study population was 3.6 months with nivolumab monotherapy and 8.0 months with combination therapy. In the roughly 70% of participants who had any degree of tumor PD-L1 expression, median PFS was 3.5 months with monotherapy, compared with 12.7 months in the combined dual therapy arms. And, in the roughly one-quarter of patients whose tumor showed at least 50% PD-L1 expression, median PFS rose to 8.3 months with nivolumab monotherapy and hasn’t yet been reached in patients on combination therapy.
The 1-year overall survival rate in patients on nivolumab monotherapy was 73% in all treated patients, 69% in those with any detectable tumor PD-L1 expression, and 83% in patients with at least 50% PD-L1 expression. In patients on combination therapy, the corresponding figures were higher at 76%, 87%, and 100%.
The clearly enhanced efficacy achieved with the combination of nivolumab plus ipilimumab was accomplished with only a modest increase in toxicity compared with nivolumab alone. At a median follow-up of 22 months in the nivolumab monotherapy group and 16 months for combination therapy, the rate of any treatment-related adverse event leading to study withdrawal was 12% with monotherapy and 18% with combination therapy.
The combination of nivolumab (Opdivo), a PD-L1 immune checkpoint inhibitor, and ipilimumab (Yervoy), a cytotoxic T-lymphocyte–associated protein 4 immune checkpoint inhibitor, is biologically attractive: “The ipilimumab primes the immune system by inducing tumor infiltration of effector T cells while depleting the number of myeloid-derived suppressor cells and suppressive regulatory T cells within the tumor microenvironment,” Dr. Gettinger explained.
Nivolumab is approved for treatment of advanced NSCLC that has progressed despite platinum-based chemotherapy. Of the various toxicities associated with the drug, only dermatologic and GI adverse events occurred more frequently with combination therapy than nivolumab alone.
There were five complete responses in the nivolumab monotherapy group and six with combination therapy. Of note, four of these complete responses occurred in patients without any measurable tumor PD-L1 expression.
Based upon these encouraging results from CheckMate 012, a phase III randomized clinical trial of nivolumab as first-line therapy in patients with advanced NSCLC is underway. In the CheckMate 227 trial, patients with any detectable PD-L1 expression are randomized to nivolumab at 3mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks, nivolumab monotherapy at 240 mg every 2 weeks, or standard platinum-based chemotherapy. Patients with no PD-L1 expression in their tumor are assigned to the nivolumab/ipilimumab combination, or nivolumab at 360 mg every 3 weeks plus chemotherapy, or chemotherapy alone.
“I think we should be cautious despite the excitement about the combination,” argued Dr. Garon, director of thoracic oncology at the University of California, Los Angeles.
He noted that various iterations of the large CheckMate 012 phase I program have been presented repeatedly at major meetings, and the shifting data have raised concerns in his mind about possible patient selection bias stemming from the study design.
“From my perspective, until we see randomized data that can control for these biases, I will remain hopeful but not yet extremely confident that this combination will be the new frontline therapy for metastatic non–small cell lung cancer,” Dr. Garon said.
Dr. Gettinger reported serving as a consultant to Bristol-Myers Squibb, which markets nivolumab.
Dr. Garon reported that his institution receives funding from Bristol-Myers Squibb as well as AstraZeneca, Boehringer Ingelheim, Eli Lilly, Genentech, Mirati, Merck, Pfizer, and Novartis.
AT WCLC 2016
Key clinical point: A combination of two immunotherapy agents with different mechanisms of action produced impressive efficacy and acceptable toxicities as first-line therapy in patients with chemotherapy-naive advanced non–small cell lung cancer.
Major finding: in patients with any detectable tumor PD-L1 expression.
Data source: This analysis from a larger phase I study included 127 patients with no prior chemotherapy for advanced NSCLC.
Disclosures: The study presenter is a consultant to Bristol-Myers Squibb, which sponsored the CheckMate 012 trial.
VIDEO: Decision aids can relay relative risks to lung cancer patients
VIENNA – Many lung cancer patients would like to work with their physicians to reach a shared decision about their care, but often feel inadequately informed to comfortably participate in the decision process.
Patient decision aids offer a way to address this knowledge and participation gap, Laurie E. Gaspar, MD, said in a video interview at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
She and her associates have run an online survey that so far has received responses from 196 lung cancer patients, caregivers of patients, or significant others of patients. One hundred seventeen (60%) said that they faced a difficult management decision, but more than half these patients said they felt they had inadequate information to make their decision. The most popular form of decision making was a shared decision with their physician, favored by 73% of the respondents, but only about half the patients believed they had actually participated in a shared-decision process with their physician, reported Dr. Gaspar, professor of radiation oncology at the University of Colorado in Aurora.
“A majority of the patients felt there was a problem in not having sufficient information, and a majority want to make decisions in a shared way,” she explained.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
VIENNA – Many lung cancer patients would like to work with their physicians to reach a shared decision about their care, but often feel inadequately informed to comfortably participate in the decision process.
Patient decision aids offer a way to address this knowledge and participation gap, Laurie E. Gaspar, MD, said in a video interview at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
She and her associates have run an online survey that so far has received responses from 196 lung cancer patients, caregivers of patients, or significant others of patients. One hundred seventeen (60%) said that they faced a difficult management decision, but more than half these patients said they felt they had inadequate information to make their decision. The most popular form of decision making was a shared decision with their physician, favored by 73% of the respondents, but only about half the patients believed they had actually participated in a shared-decision process with their physician, reported Dr. Gaspar, professor of radiation oncology at the University of Colorado in Aurora.
“A majority of the patients felt there was a problem in not having sufficient information, and a majority want to make decisions in a shared way,” she explained.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
VIENNA – Many lung cancer patients would like to work with their physicians to reach a shared decision about their care, but often feel inadequately informed to comfortably participate in the decision process.
Patient decision aids offer a way to address this knowledge and participation gap, Laurie E. Gaspar, MD, said in a video interview at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
She and her associates have run an online survey that so far has received responses from 196 lung cancer patients, caregivers of patients, or significant others of patients. One hundred seventeen (60%) said that they faced a difficult management decision, but more than half these patients said they felt they had inadequate information to make their decision. The most popular form of decision making was a shared decision with their physician, favored by 73% of the respondents, but only about half the patients believed they had actually participated in a shared-decision process with their physician, reported Dr. Gaspar, professor of radiation oncology at the University of Colorado in Aurora.
“A majority of the patients felt there was a problem in not having sufficient information, and a majority want to make decisions in a shared way,” she explained.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
At WCLC 2016
Key clinical point:
Major finding: A shared-decision process received support from 73% of patients, but just half believed they participated in shared decision making.
Data source: Online survey completed by 196 lung cancer patients, caregivers or significant others.
Disclosures: Dr. Gaspar had no disclosures.
Centers of excellence program raises quality bar in lung cancer management
VIENNA – A grassroots, patient-centric program aimed at encouraging U.S. community hospitals in underserved areas to adopt a comprehensive centers-of-excellence model for treatment of lung cancer has demonstrated that community cancer centers can achieve quality of care comparable to that found in academic medical centers, Raymond Osarogiagbon, MD, declared at the World Congress on Lung Cancer.
One major reason why aggregate lung cancer survival in the United States has barely inched upward during the past 3 decades is there is often a huge gap between the quality of care patients get at academic research centers – including access to clinical trials – and what they can get in community hospitals. Eighty percent of lung cancer patients receive their care in these community cancer centers, where not all physicians and surgeons may be up to speed with guideline-recommended best practices, observed Dr. Osarogiagbon, a medical oncologist and director of the multidisciplinary thoracic oncology program at Baptist Cancer Center in Memphis.
The centers of excellence program, supported by the Bonnie J. Addario Lung Cancer Foundation, is an attempt to address this disparity. In 3 years, 13 hospitals in areas with large underserved patient populations in nine states have qualified. Dr. Osarogiagbon anticipates that the competitive advantage this designation provides will spur more and more community hospitals with cancer centers to get on board.
To qualify, community cancer centers have to commit to following specific best practices as standards of care in accord with guidelines issued by groups including the National Comprehensive Cancer Network and the American Society of Clinical Oncology. Requirements include the use of multidisciplinary teams for treatment decisions, routine use of molecular diagnostics and targeted therapies, patient access to clinical trials, longitudinal institutional data tracking, patient and caregiver education programs, and minimally invasive surgical and staging techniques. A lung cancer screening program is required. So is a systematic program for management of all incidentally detected lung nodules, many of which today fall between the cracks.
In an interview, Dr. Osarogiagbon shared several examples of how achieving the foundation’s center of excellence designation enables community cancer centers to achieve top-quality care on a par with academic medical centers. At Memorial Cancer Institute in Hollywood, Fla., which serves large Hispanic and black populations, implementation of a lung cancer screening program and other measures has resulted in 40% of patients with lung cancer being diagnosed with stage 1 or 2 disease amenable to curative surgery. The overall U.S. rate is significantly lower at 29%.
And in an area composed of western Tennessee, northern Mississippi, and eastern Arkansas, Dr. Osarogiagbon and coinvestigators at the Baptist Cancer Center conducted a study demonstrating that the use of two complementary surgical staging interventions resulted in improved rates of guideline-recommended surgical staging quality.
The observational study, presented elsewhere at the world congress by Nicholas Faris, MD, of the Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, entailed analysis of curative-intent resections in 2,094 patients with non–small-cell lung cancer during 2004-2016. A novel anatomically sound gross dissection protocol was provided to assist pathologists in retrieving the intrapulmonary lymph nodes required for staging in 161 patients undergoing curative resection. A special lymph node specimen collection kit was utilized in 152. Another 289 resections utilized both interventions. And 1,492 patients received neither intervention.
Use of the interventions was associated with higher rates of adherence to various professional organizations’ guidelines for high-quality surgical staging. For example, the American College of Surgeons Commission on Cancer recommends that at least 10 lymph nodes be examined in patients with stage 1a-2b NSCLC. This was achieved in 71% of patients who had both interventions, 56% of those where the lymph node specimen collection kit was utilized but not the pathology intervention, 48% of patients where the pathology intervention but not the kit was employed, and in only 25% of patients where neither was used.
Similarly, more than three mediastinal lymph node stations were sampled in accord with National Comprehensive Cancer Network guidelines in 96% of patients with both interventions, 90% with the lymph node collection kit, 54% with the pathology intervention, and only 44% with neither, Dr. Osarogiagbon said in the interview.
Dr. Osarogiagbon reported serving as a consultant to Eli Lilly, Genentech, and the Association of Community Cancer Centers.
VIENNA – A grassroots, patient-centric program aimed at encouraging U.S. community hospitals in underserved areas to adopt a comprehensive centers-of-excellence model for treatment of lung cancer has demonstrated that community cancer centers can achieve quality of care comparable to that found in academic medical centers, Raymond Osarogiagbon, MD, declared at the World Congress on Lung Cancer.
One major reason why aggregate lung cancer survival in the United States has barely inched upward during the past 3 decades is there is often a huge gap between the quality of care patients get at academic research centers – including access to clinical trials – and what they can get in community hospitals. Eighty percent of lung cancer patients receive their care in these community cancer centers, where not all physicians and surgeons may be up to speed with guideline-recommended best practices, observed Dr. Osarogiagbon, a medical oncologist and director of the multidisciplinary thoracic oncology program at Baptist Cancer Center in Memphis.
The centers of excellence program, supported by the Bonnie J. Addario Lung Cancer Foundation, is an attempt to address this disparity. In 3 years, 13 hospitals in areas with large underserved patient populations in nine states have qualified. Dr. Osarogiagbon anticipates that the competitive advantage this designation provides will spur more and more community hospitals with cancer centers to get on board.
To qualify, community cancer centers have to commit to following specific best practices as standards of care in accord with guidelines issued by groups including the National Comprehensive Cancer Network and the American Society of Clinical Oncology. Requirements include the use of multidisciplinary teams for treatment decisions, routine use of molecular diagnostics and targeted therapies, patient access to clinical trials, longitudinal institutional data tracking, patient and caregiver education programs, and minimally invasive surgical and staging techniques. A lung cancer screening program is required. So is a systematic program for management of all incidentally detected lung nodules, many of which today fall between the cracks.
In an interview, Dr. Osarogiagbon shared several examples of how achieving the foundation’s center of excellence designation enables community cancer centers to achieve top-quality care on a par with academic medical centers. At Memorial Cancer Institute in Hollywood, Fla., which serves large Hispanic and black populations, implementation of a lung cancer screening program and other measures has resulted in 40% of patients with lung cancer being diagnosed with stage 1 or 2 disease amenable to curative surgery. The overall U.S. rate is significantly lower at 29%.
And in an area composed of western Tennessee, northern Mississippi, and eastern Arkansas, Dr. Osarogiagbon and coinvestigators at the Baptist Cancer Center conducted a study demonstrating that the use of two complementary surgical staging interventions resulted in improved rates of guideline-recommended surgical staging quality.
The observational study, presented elsewhere at the world congress by Nicholas Faris, MD, of the Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, entailed analysis of curative-intent resections in 2,094 patients with non–small-cell lung cancer during 2004-2016. A novel anatomically sound gross dissection protocol was provided to assist pathologists in retrieving the intrapulmonary lymph nodes required for staging in 161 patients undergoing curative resection. A special lymph node specimen collection kit was utilized in 152. Another 289 resections utilized both interventions. And 1,492 patients received neither intervention.
Use of the interventions was associated with higher rates of adherence to various professional organizations’ guidelines for high-quality surgical staging. For example, the American College of Surgeons Commission on Cancer recommends that at least 10 lymph nodes be examined in patients with stage 1a-2b NSCLC. This was achieved in 71% of patients who had both interventions, 56% of those where the lymph node specimen collection kit was utilized but not the pathology intervention, 48% of patients where the pathology intervention but not the kit was employed, and in only 25% of patients where neither was used.
Similarly, more than three mediastinal lymph node stations were sampled in accord with National Comprehensive Cancer Network guidelines in 96% of patients with both interventions, 90% with the lymph node collection kit, 54% with the pathology intervention, and only 44% with neither, Dr. Osarogiagbon said in the interview.
Dr. Osarogiagbon reported serving as a consultant to Eli Lilly, Genentech, and the Association of Community Cancer Centers.
VIENNA – A grassroots, patient-centric program aimed at encouraging U.S. community hospitals in underserved areas to adopt a comprehensive centers-of-excellence model for treatment of lung cancer has demonstrated that community cancer centers can achieve quality of care comparable to that found in academic medical centers, Raymond Osarogiagbon, MD, declared at the World Congress on Lung Cancer.
One major reason why aggregate lung cancer survival in the United States has barely inched upward during the past 3 decades is there is often a huge gap between the quality of care patients get at academic research centers – including access to clinical trials – and what they can get in community hospitals. Eighty percent of lung cancer patients receive their care in these community cancer centers, where not all physicians and surgeons may be up to speed with guideline-recommended best practices, observed Dr. Osarogiagbon, a medical oncologist and director of the multidisciplinary thoracic oncology program at Baptist Cancer Center in Memphis.
The centers of excellence program, supported by the Bonnie J. Addario Lung Cancer Foundation, is an attempt to address this disparity. In 3 years, 13 hospitals in areas with large underserved patient populations in nine states have qualified. Dr. Osarogiagbon anticipates that the competitive advantage this designation provides will spur more and more community hospitals with cancer centers to get on board.
To qualify, community cancer centers have to commit to following specific best practices as standards of care in accord with guidelines issued by groups including the National Comprehensive Cancer Network and the American Society of Clinical Oncology. Requirements include the use of multidisciplinary teams for treatment decisions, routine use of molecular diagnostics and targeted therapies, patient access to clinical trials, longitudinal institutional data tracking, patient and caregiver education programs, and minimally invasive surgical and staging techniques. A lung cancer screening program is required. So is a systematic program for management of all incidentally detected lung nodules, many of which today fall between the cracks.
In an interview, Dr. Osarogiagbon shared several examples of how achieving the foundation’s center of excellence designation enables community cancer centers to achieve top-quality care on a par with academic medical centers. At Memorial Cancer Institute in Hollywood, Fla., which serves large Hispanic and black populations, implementation of a lung cancer screening program and other measures has resulted in 40% of patients with lung cancer being diagnosed with stage 1 or 2 disease amenable to curative surgery. The overall U.S. rate is significantly lower at 29%.
And in an area composed of western Tennessee, northern Mississippi, and eastern Arkansas, Dr. Osarogiagbon and coinvestigators at the Baptist Cancer Center conducted a study demonstrating that the use of two complementary surgical staging interventions resulted in improved rates of guideline-recommended surgical staging quality.
The observational study, presented elsewhere at the world congress by Nicholas Faris, MD, of the Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, entailed analysis of curative-intent resections in 2,094 patients with non–small-cell lung cancer during 2004-2016. A novel anatomically sound gross dissection protocol was provided to assist pathologists in retrieving the intrapulmonary lymph nodes required for staging in 161 patients undergoing curative resection. A special lymph node specimen collection kit was utilized in 152. Another 289 resections utilized both interventions. And 1,492 patients received neither intervention.
Use of the interventions was associated with higher rates of adherence to various professional organizations’ guidelines for high-quality surgical staging. For example, the American College of Surgeons Commission on Cancer recommends that at least 10 lymph nodes be examined in patients with stage 1a-2b NSCLC. This was achieved in 71% of patients who had both interventions, 56% of those where the lymph node specimen collection kit was utilized but not the pathology intervention, 48% of patients where the pathology intervention but not the kit was employed, and in only 25% of patients where neither was used.
Similarly, more than three mediastinal lymph node stations were sampled in accord with National Comprehensive Cancer Network guidelines in 96% of patients with both interventions, 90% with the lymph node collection kit, 54% with the pathology intervention, and only 44% with neither, Dr. Osarogiagbon said in the interview.
Dr. Osarogiagbon reported serving as a consultant to Eli Lilly, Genentech, and the Association of Community Cancer Centers.
EXPERT ANALYSIS FROM WCLC 2016
Checkpoint inhibitors for lung cancer figure prominently at WCLC 2016
Oncology Practice will be on-site this coming week at the 17th World Conference on Lung Cancer in Vienna with the latest on checkpoint inhibitors and other treatments for lung cancer. Look for coverage of the best clinical presentations at the conference, hosted by the International Association for the Study of Lung Cancer, including the following and more, beginning Sunday, Dec. 4.
OA03.01 - First-Line Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Patients With Advanced NSCLC: Long-Term Outcomes from CheckMate 012.
OA03.02 - Atezolizumab as 1L Therapy for Advanced NSCLC in PD-L1–Selected Patients: Updated ORR, PFS, and OS Data From the BIRCH Study.
OA03.03 - JAVELIN Solid Tumor: Safety and Clinical Activity of Avelumab (Anti–PD-L1) as First-Line Treatment in Patients With Advanced NSCLC.
OA03.05 - Analysis of Early Survival in Patients With Advanced Nonsquamous NSCLC Treated With Nivolumab vs. Docetaxel in CheckMate 057.
OA03.07 - KEYNOTE-010: Durable Clinical Benefit in Patients With Previously Treated, PD-L1–Expressing NSCLC Who Completed Pembrolizumab.
OA05.01 - Pembrolizumab in Patients With Extensive-Stage Small Cell Lung Cancer: Updated Survival Results from KEYNOTE-028.
OA13.03 - Long-Term Overall Survival for Patients With Malignant Pleural Mesothelioma on Pembrolizumab Enrolled in KEYNOTE-028.
PL03.03 - Randomised Phase III Study of Osimertinib vs. Platinum-Pemetrexed for EGFR T790M-Positive Advanced NSCLC (AURA3).
PL03.05 - BRAIN: A Phase III Trial Comparing WBI and Chemotherapy With Icotinib in NSCLC With Brain Metastases Harboring EGFR Mutations (CTONG 1201).
PL03.07 - First-line Ceritinib Versus Chemotherapy in Patients With ALK-Rearranged (ALK+) NSCLC: A Randomized, Phase III Study (ASCEND-4).
PL03.09 - Phase III Study of Ganetespib, a Heat Shock Protein 90 Inhibitor, With Docetaxel versus Docetaxel in Advanced Non–Small Cell Lung Cancer (GALAXY-2).
PL04a.01 - Health-Related Quality of Life for Pembrolizumab vs. Chemotherapy in Advanced NSCLC With PD-L1 TPS Greater Than or Equal to 50%: Data From KEYNOTE-024.
PL04a.02 - OAK, a Randomized Phase III Study of Atezolizumab vs. Docetaxel in Patients With Advanced NSCLC: Results From Subgroup Analyses.
PL04a.03 - Durvalumab in 3rd-Line Locally Advanced or Metastatic, EGFR/ALK Wild-Type NSCLC: Results from the Phase II ATLANTIC Study.
MA09.02 - Pembrolizumab + Carboplatin and Pemetrexed as 1st-Line Therapy for Advanced Non–Small Cell Lung Cancer: KEYNOTE-021.
MA09.11 - Efficacy and Safety of Necitumumab and Pembrolizumab Combination Therapy in Stage IV Nonsquamous Non–Small Cell Lung Cancer.
Oncology Practice will be on-site this coming week at the 17th World Conference on Lung Cancer in Vienna with the latest on checkpoint inhibitors and other treatments for lung cancer. Look for coverage of the best clinical presentations at the conference, hosted by the International Association for the Study of Lung Cancer, including the following and more, beginning Sunday, Dec. 4.
OA03.01 - First-Line Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Patients With Advanced NSCLC: Long-Term Outcomes from CheckMate 012.
OA03.02 - Atezolizumab as 1L Therapy for Advanced NSCLC in PD-L1–Selected Patients: Updated ORR, PFS, and OS Data From the BIRCH Study.
OA03.03 - JAVELIN Solid Tumor: Safety and Clinical Activity of Avelumab (Anti–PD-L1) as First-Line Treatment in Patients With Advanced NSCLC.
OA03.05 - Analysis of Early Survival in Patients With Advanced Nonsquamous NSCLC Treated With Nivolumab vs. Docetaxel in CheckMate 057.
OA03.07 - KEYNOTE-010: Durable Clinical Benefit in Patients With Previously Treated, PD-L1–Expressing NSCLC Who Completed Pembrolizumab.
OA05.01 - Pembrolizumab in Patients With Extensive-Stage Small Cell Lung Cancer: Updated Survival Results from KEYNOTE-028.
OA13.03 - Long-Term Overall Survival for Patients With Malignant Pleural Mesothelioma on Pembrolizumab Enrolled in KEYNOTE-028.
PL03.03 - Randomised Phase III Study of Osimertinib vs. Platinum-Pemetrexed for EGFR T790M-Positive Advanced NSCLC (AURA3).
PL03.05 - BRAIN: A Phase III Trial Comparing WBI and Chemotherapy With Icotinib in NSCLC With Brain Metastases Harboring EGFR Mutations (CTONG 1201).
PL03.07 - First-line Ceritinib Versus Chemotherapy in Patients With ALK-Rearranged (ALK+) NSCLC: A Randomized, Phase III Study (ASCEND-4).
PL03.09 - Phase III Study of Ganetespib, a Heat Shock Protein 90 Inhibitor, With Docetaxel versus Docetaxel in Advanced Non–Small Cell Lung Cancer (GALAXY-2).
PL04a.01 - Health-Related Quality of Life for Pembrolizumab vs. Chemotherapy in Advanced NSCLC With PD-L1 TPS Greater Than or Equal to 50%: Data From KEYNOTE-024.
PL04a.02 - OAK, a Randomized Phase III Study of Atezolizumab vs. Docetaxel in Patients With Advanced NSCLC: Results From Subgroup Analyses.
PL04a.03 - Durvalumab in 3rd-Line Locally Advanced or Metastatic, EGFR/ALK Wild-Type NSCLC: Results from the Phase II ATLANTIC Study.
MA09.02 - Pembrolizumab + Carboplatin and Pemetrexed as 1st-Line Therapy for Advanced Non–Small Cell Lung Cancer: KEYNOTE-021.
MA09.11 - Efficacy and Safety of Necitumumab and Pembrolizumab Combination Therapy in Stage IV Nonsquamous Non–Small Cell Lung Cancer.
Oncology Practice will be on-site this coming week at the 17th World Conference on Lung Cancer in Vienna with the latest on checkpoint inhibitors and other treatments for lung cancer. Look for coverage of the best clinical presentations at the conference, hosted by the International Association for the Study of Lung Cancer, including the following and more, beginning Sunday, Dec. 4.
OA03.01 - First-Line Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Patients With Advanced NSCLC: Long-Term Outcomes from CheckMate 012.
OA03.02 - Atezolizumab as 1L Therapy for Advanced NSCLC in PD-L1–Selected Patients: Updated ORR, PFS, and OS Data From the BIRCH Study.
OA03.03 - JAVELIN Solid Tumor: Safety and Clinical Activity of Avelumab (Anti–PD-L1) as First-Line Treatment in Patients With Advanced NSCLC.
OA03.05 - Analysis of Early Survival in Patients With Advanced Nonsquamous NSCLC Treated With Nivolumab vs. Docetaxel in CheckMate 057.
OA03.07 - KEYNOTE-010: Durable Clinical Benefit in Patients With Previously Treated, PD-L1–Expressing NSCLC Who Completed Pembrolizumab.
OA05.01 - Pembrolizumab in Patients With Extensive-Stage Small Cell Lung Cancer: Updated Survival Results from KEYNOTE-028.
OA13.03 - Long-Term Overall Survival for Patients With Malignant Pleural Mesothelioma on Pembrolizumab Enrolled in KEYNOTE-028.
PL03.03 - Randomised Phase III Study of Osimertinib vs. Platinum-Pemetrexed for EGFR T790M-Positive Advanced NSCLC (AURA3).
PL03.05 - BRAIN: A Phase III Trial Comparing WBI and Chemotherapy With Icotinib in NSCLC With Brain Metastases Harboring EGFR Mutations (CTONG 1201).
PL03.07 - First-line Ceritinib Versus Chemotherapy in Patients With ALK-Rearranged (ALK+) NSCLC: A Randomized, Phase III Study (ASCEND-4).
PL03.09 - Phase III Study of Ganetespib, a Heat Shock Protein 90 Inhibitor, With Docetaxel versus Docetaxel in Advanced Non–Small Cell Lung Cancer (GALAXY-2).
PL04a.01 - Health-Related Quality of Life for Pembrolizumab vs. Chemotherapy in Advanced NSCLC With PD-L1 TPS Greater Than or Equal to 50%: Data From KEYNOTE-024.
PL04a.02 - OAK, a Randomized Phase III Study of Atezolizumab vs. Docetaxel in Patients With Advanced NSCLC: Results From Subgroup Analyses.
PL04a.03 - Durvalumab in 3rd-Line Locally Advanced or Metastatic, EGFR/ALK Wild-Type NSCLC: Results from the Phase II ATLANTIC Study.
MA09.02 - Pembrolizumab + Carboplatin and Pemetrexed as 1st-Line Therapy for Advanced Non–Small Cell Lung Cancer: KEYNOTE-021.
MA09.11 - Efficacy and Safety of Necitumumab and Pembrolizumab Combination Therapy in Stage IV Nonsquamous Non–Small Cell Lung Cancer.
FROM WCLC 2016
In lung cancer screening, patient education works
A counseling and shared decision-making visit improved patient knowledge of the eligibility criteria, benefits, and potential risks of lung cancer screening via a low-radiation chest CT scan.
The Center for Medicare & Medicaid Services has added the type of visit addressed in this study to Medicare’s preventive services benefits for individuals meeting certain criteria, but no previous study had looked at how the implementation of such a visit impacted a patient’s knowledge and understanding.
The researchers noted significant improvement in all questions before and after a counseling session (P = .03 to P less than .0001). Those improvements lessened at 1 month, but were still higher than precounseling scores.
The percentages of participants who knew the age criteria for lung cancer screening before counseling, immediately after counseling, and 1 month after counseling, for example, were 8.8% (11 patients), 59.2% (74 patients), and 21.4% (24 patients), respectively. The percentage of participants able to identify at least one of the potential hazards of screening increased by a similar amount immediately after receiving counseling, as did the percentage of participants able to identify the age criteria for lung cancer screening immediately after receiving counseling. The percentages of patients able to identify at least one of the potential hazards of screening were 38.4% before counseling and 90.4% immediately after receiving counseling. One month following counseling, the percentage of patients with such knowledge remained fairly high, dropping to 78.6%.
“Showing the value of these visits is very important to encourage policymakers and payers to continue to support the counseling and shared decision-making visit,” Peter J. Mazzone, MD, MPH, who led the study, said in an interview.
These types of conversations are important because of the uncertainties surrounding lung cancer screening, which leads to about a 20% reduction in mortality risk. That translates to the need to screen about 250 people to save 1 life. “I think the public sometimes doesn’t realize that the effectiveness of some of these preventive screenings may not be as large as they think they are,” said David Grossman, vice chair of the US Preventive Services Task Force and a senior investigator at the Group Health Research Institute, Seattle, who was not involved in the study.
The researchers developed a centralized counseling and shared decision-making visit that included a narrated slide show and individualized risk assessment. They approached 423 consecutive patients who had been identified by their primary care provider or a specialist as potential candidates for screening. Of those 423 patients, 125 agreed to participate in the study (Chest. 2016 Nov 1. doi: 10.1016/j.chest.2016.10.027).
The session delivered expected improvements in patient knowledge, but there were some surprises. “The starting point of knowledge was perhaps less than we would have anticipated, and the gains, though very substantial, weren’t perfect,” said Dr. Mazzone, who is also director of the lung cancer screening program at the Cleveland Clinic.
The drop in knowledge at 1 month suggests that the information needs to be reinforced, possibly each time patients come in for an annual screening visit, Dr. Mazzone added.
Counseling sessions can also help convince patients to quit smoking, if tobacco use is a concern. “It’s not appropriate to screen for lung cancer without making a commitment to try to quit,” said Dr. Grossman.
No funding source was disclosed. Dr. Mazzone and Dr. Grossman reported having no financial disclosures.
A counseling and shared decision-making visit improved patient knowledge of the eligibility criteria, benefits, and potential risks of lung cancer screening via a low-radiation chest CT scan.
The Center for Medicare & Medicaid Services has added the type of visit addressed in this study to Medicare’s preventive services benefits for individuals meeting certain criteria, but no previous study had looked at how the implementation of such a visit impacted a patient’s knowledge and understanding.
The researchers noted significant improvement in all questions before and after a counseling session (P = .03 to P less than .0001). Those improvements lessened at 1 month, but were still higher than precounseling scores.
The percentages of participants who knew the age criteria for lung cancer screening before counseling, immediately after counseling, and 1 month after counseling, for example, were 8.8% (11 patients), 59.2% (74 patients), and 21.4% (24 patients), respectively. The percentage of participants able to identify at least one of the potential hazards of screening increased by a similar amount immediately after receiving counseling, as did the percentage of participants able to identify the age criteria for lung cancer screening immediately after receiving counseling. The percentages of patients able to identify at least one of the potential hazards of screening were 38.4% before counseling and 90.4% immediately after receiving counseling. One month following counseling, the percentage of patients with such knowledge remained fairly high, dropping to 78.6%.
“Showing the value of these visits is very important to encourage policymakers and payers to continue to support the counseling and shared decision-making visit,” Peter J. Mazzone, MD, MPH, who led the study, said in an interview.
These types of conversations are important because of the uncertainties surrounding lung cancer screening, which leads to about a 20% reduction in mortality risk. That translates to the need to screen about 250 people to save 1 life. “I think the public sometimes doesn’t realize that the effectiveness of some of these preventive screenings may not be as large as they think they are,” said David Grossman, vice chair of the US Preventive Services Task Force and a senior investigator at the Group Health Research Institute, Seattle, who was not involved in the study.
The researchers developed a centralized counseling and shared decision-making visit that included a narrated slide show and individualized risk assessment. They approached 423 consecutive patients who had been identified by their primary care provider or a specialist as potential candidates for screening. Of those 423 patients, 125 agreed to participate in the study (Chest. 2016 Nov 1. doi: 10.1016/j.chest.2016.10.027).
The session delivered expected improvements in patient knowledge, but there were some surprises. “The starting point of knowledge was perhaps less than we would have anticipated, and the gains, though very substantial, weren’t perfect,” said Dr. Mazzone, who is also director of the lung cancer screening program at the Cleveland Clinic.
The drop in knowledge at 1 month suggests that the information needs to be reinforced, possibly each time patients come in for an annual screening visit, Dr. Mazzone added.
Counseling sessions can also help convince patients to quit smoking, if tobacco use is a concern. “It’s not appropriate to screen for lung cancer without making a commitment to try to quit,” said Dr. Grossman.
No funding source was disclosed. Dr. Mazzone and Dr. Grossman reported having no financial disclosures.
A counseling and shared decision-making visit improved patient knowledge of the eligibility criteria, benefits, and potential risks of lung cancer screening via a low-radiation chest CT scan.
The Center for Medicare & Medicaid Services has added the type of visit addressed in this study to Medicare’s preventive services benefits for individuals meeting certain criteria, but no previous study had looked at how the implementation of such a visit impacted a patient’s knowledge and understanding.
The researchers noted significant improvement in all questions before and after a counseling session (P = .03 to P less than .0001). Those improvements lessened at 1 month, but were still higher than precounseling scores.
The percentages of participants who knew the age criteria for lung cancer screening before counseling, immediately after counseling, and 1 month after counseling, for example, were 8.8% (11 patients), 59.2% (74 patients), and 21.4% (24 patients), respectively. The percentage of participants able to identify at least one of the potential hazards of screening increased by a similar amount immediately after receiving counseling, as did the percentage of participants able to identify the age criteria for lung cancer screening immediately after receiving counseling. The percentages of patients able to identify at least one of the potential hazards of screening were 38.4% before counseling and 90.4% immediately after receiving counseling. One month following counseling, the percentage of patients with such knowledge remained fairly high, dropping to 78.6%.
“Showing the value of these visits is very important to encourage policymakers and payers to continue to support the counseling and shared decision-making visit,” Peter J. Mazzone, MD, MPH, who led the study, said in an interview.
These types of conversations are important because of the uncertainties surrounding lung cancer screening, which leads to about a 20% reduction in mortality risk. That translates to the need to screen about 250 people to save 1 life. “I think the public sometimes doesn’t realize that the effectiveness of some of these preventive screenings may not be as large as they think they are,” said David Grossman, vice chair of the US Preventive Services Task Force and a senior investigator at the Group Health Research Institute, Seattle, who was not involved in the study.
The researchers developed a centralized counseling and shared decision-making visit that included a narrated slide show and individualized risk assessment. They approached 423 consecutive patients who had been identified by their primary care provider or a specialist as potential candidates for screening. Of those 423 patients, 125 agreed to participate in the study (Chest. 2016 Nov 1. doi: 10.1016/j.chest.2016.10.027).
The session delivered expected improvements in patient knowledge, but there were some surprises. “The starting point of knowledge was perhaps less than we would have anticipated, and the gains, though very substantial, weren’t perfect,” said Dr. Mazzone, who is also director of the lung cancer screening program at the Cleveland Clinic.
The drop in knowledge at 1 month suggests that the information needs to be reinforced, possibly each time patients come in for an annual screening visit, Dr. Mazzone added.
Counseling sessions can also help convince patients to quit smoking, if tobacco use is a concern. “It’s not appropriate to screen for lung cancer without making a commitment to try to quit,” said Dr. Grossman.
No funding source was disclosed. Dr. Mazzone and Dr. Grossman reported having no financial disclosures.
FROM CHEST
Key clinical point:
Major finding: Failure to identify potential harm dropped from 61.6% to 21.4%.
Data source: Prospective study of 125 patients.
Disclosures: No funding source was disclosed. Dr. Mazzone and Dr. Grossman reported having no financial disclosures.