Breast Cancer

A “favorable” lifestyle was associated with a reduced risk of breast cancer even among women at high genetic risk for the disease in a study of more than 90,000 women, researchers reported.

The findings suggest that, regardless of genetic risk, women may be able to reduce their risk of developing breast cancer by getting adequate levels of exercise; maintaining a healthy weight; and limiting or eliminating use of alcohol, oral contraceptives, and hormone replacement therapy.

Kawthar Al Ajmi, MSc, of the University of Manchester (England), and colleagues published these findings in JAMA Network Open.

With almost a quarter of breast cancers thought to be preventable in the United Kingdom, “it is important to understand the contribution of modifiable risk factors ... and how they affect or add to the inherited genetic factors,” the researchers wrote.

To that end, the team reviewed 91,217 white, postmenopausal women in the United Kingdom Biobank, an ongoing longitudinal study of the contribution of genetic, environmental, and lifestyle risk factors in disease. There were 2,728 women who developed breast cancer at a median follow-up of 10 years.

The investigators used a polygenic risk score to categorize subjects as low, intermediate, or high genetic risk. The score was constructed using 305 single-nucleotide variants.

Within each risk group, the researchers divided women by the presence or absence of five lifestyle factors previously associated with a lower risk of breast cancer: healthy weight, regular exercise, no use of hormone replacement therapy beyond 5 years, no oral contraceptive use, and alcohol intake no more than twice a week.

Women with four or more of these factors were deemed to have a favorable lifestyle. Women with two or three factors had an intermediate lifestyle, and women with fewer factors had an unfavorable lifestyle.
 

Results

The data showed an association between breast cancer and a body mass index of 25 or higher (relative risk, 1.14), no regular physical activity (RR, 1.12), alcohol intake at least three times per week (RR, 1.11), and use of hormone replacement therapy for 5 or more years (RR, 1.23). History of oral contraceptive use was not associated with breast cancer risk (RR, 1.02), but this factor remained a part of the lifestyle classification.

In the low genetic risk group, an intermediate lifestyle (hazard ratio, 1.40; 95% CI, 1.09-1.80) and an unfavorable lifestyle (HR, 1.63; 95% CI, 1.14-2.34) were both associated with a higher risk of breast cancer, compared with a favorable lifestyle.

In the intermediate genetic risk group, intermediate (HR, 1.37; 95% CI, 1.12-1.68) and unfavorable lifestyles (HR 1.94; 95% CI, 1.46-2.58) were again associated with higher breast cancer risk, compared with a favorable lifestyle .

Even in the high genetic risk group, intermediate (HR, 1.13; 95% CI, 0.98-1.31) and unfavorable lifestyles (HR, 1.39; 95% CI, 1.11-1.74) were associated with increased breast cancer risk. Results were adjusted for both age and family history.

In the end, “a healthier lifestyle ... appeared to be associated with a reduced level of risk for [breast cancer], even if the women were at higher genetic risk,” the researchers wrote. “Our findings suggest that women may be able to alter or reduce their risk of developing [breast cancer] by following healthier lifestyles,” regardless of genetic predisposition.
 

‘Surprising’ findings

It’s “surprising that these lifestyle changes lowered the risk of breast cancer,” said Charles Shapiro, MD, of the Icahn School of Medicine at Mount Sinai in New York, who was not involved in this study.

The study “requires replication,” he said. “On the other hand, these lifestyle changes promote overall health and certainly are associated with decreased risks of cardiovascular disease, the number one killer of women.”

“Patients always want to know what they can do above and beyond screening mammograms to reduce their risk of developing breast cancer,” said William Gradishar, MD, of Northwestern University in Chicago, who was not involved in the study.

“These data should empower patients that they can impact on their overall health and reduce the risk of developing breast cancer,” he said.

Among the study’s limitations, it’s unclear how the findings apply to nonwhite, nonpostmenopausal women, and the analysis did not differentiate between breast cancer subtypes.

In addition, although oral contraceptives have been linked to breast cancer in the past, there was no association in this study. Possible explanations could be that the investigators did not take into account duration of use, age of last use, and type or oral contraceptive used, they noted.

This research was funded by the National Institute for Health Research Manchester Biomedical Research Centre, the Alan Turing Institute, and a Cancer Research UK Integrated Cancer Epidemiology Programme grant. The investigators, Dr. Gradishar, and Dr. Shapiro have no relevant disclosures.

aotto@mdedge.com

SOURCE: Al Ajmi K et al. JAMA Netw Open. 2020;3(4):e203760.

A “favorable” lifestyle was associated with a reduced risk of breast cancer even among women at high genetic risk for the disease in a study of more than 90,000 women, researchers reported.

The findings suggest that, regardless of genetic risk, women may be able to reduce their risk of developing breast cancer by getting adequate levels of exercise; maintaining a healthy weight; and limiting or eliminating use of alcohol, oral contraceptives, and hormone replacement therapy.

Kawthar Al Ajmi, MSc, of the University of Manchester (England), and colleagues published these findings in JAMA Network Open.

With almost a quarter of breast cancers thought to be preventable in the United Kingdom, “it is important to understand the contribution of modifiable risk factors ... and how they affect or add to the inherited genetic factors,” the researchers wrote.

To that end, the team reviewed 91,217 white, postmenopausal women in the United Kingdom Biobank, an ongoing longitudinal study of the contribution of genetic, environmental, and lifestyle risk factors in disease. There were 2,728 women who developed breast cancer at a median follow-up of 10 years.

The investigators used a polygenic risk score to categorize subjects as low, intermediate, or high genetic risk. The score was constructed using 305 single-nucleotide variants.

Within each risk group, the researchers divided women by the presence or absence of five lifestyle factors previously associated with a lower risk of breast cancer: healthy weight, regular exercise, no use of hormone replacement therapy beyond 5 years, no oral contraceptive use, and alcohol intake no more than twice a week.

Women with four or more of these factors were deemed to have a favorable lifestyle. Women with two or three factors had an intermediate lifestyle, and women with fewer factors had an unfavorable lifestyle.
 

Results

The data showed an association between breast cancer and a body mass index of 25 or higher (relative risk, 1.14), no regular physical activity (RR, 1.12), alcohol intake at least three times per week (RR, 1.11), and use of hormone replacement therapy for 5 or more years (RR, 1.23). History of oral contraceptive use was not associated with breast cancer risk (RR, 1.02), but this factor remained a part of the lifestyle classification.

In the low genetic risk group, an intermediate lifestyle (hazard ratio, 1.40; 95% CI, 1.09-1.80) and an unfavorable lifestyle (HR, 1.63; 95% CI, 1.14-2.34) were both associated with a higher risk of breast cancer, compared with a favorable lifestyle.

In the intermediate genetic risk group, intermediate (HR, 1.37; 95% CI, 1.12-1.68) and unfavorable lifestyles (HR 1.94; 95% CI, 1.46-2.58) were again associated with higher breast cancer risk, compared with a favorable lifestyle .

Even in the high genetic risk group, intermediate (HR, 1.13; 95% CI, 0.98-1.31) and unfavorable lifestyles (HR, 1.39; 95% CI, 1.11-1.74) were associated with increased breast cancer risk. Results were adjusted for both age and family history.

In the end, “a healthier lifestyle ... appeared to be associated with a reduced level of risk for [breast cancer], even if the women were at higher genetic risk,” the researchers wrote. “Our findings suggest that women may be able to alter or reduce their risk of developing [breast cancer] by following healthier lifestyles,” regardless of genetic predisposition.
 

‘Surprising’ findings

It’s “surprising that these lifestyle changes lowered the risk of breast cancer,” said Charles Shapiro, MD, of the Icahn School of Medicine at Mount Sinai in New York, who was not involved in this study.

The study “requires replication,” he said. “On the other hand, these lifestyle changes promote overall health and certainly are associated with decreased risks of cardiovascular disease, the number one killer of women.”

“Patients always want to know what they can do above and beyond screening mammograms to reduce their risk of developing breast cancer,” said William Gradishar, MD, of Northwestern University in Chicago, who was not involved in the study.

“These data should empower patients that they can impact on their overall health and reduce the risk of developing breast cancer,” he said.

Among the study’s limitations, it’s unclear how the findings apply to nonwhite, nonpostmenopausal women, and the analysis did not differentiate between breast cancer subtypes.

In addition, although oral contraceptives have been linked to breast cancer in the past, there was no association in this study. Possible explanations could be that the investigators did not take into account duration of use, age of last use, and type or oral contraceptive used, they noted.

This research was funded by the National Institute for Health Research Manchester Biomedical Research Centre, the Alan Turing Institute, and a Cancer Research UK Integrated Cancer Epidemiology Programme grant. The investigators, Dr. Gradishar, and Dr. Shapiro have no relevant disclosures.

aotto@mdedge.com

SOURCE: Al Ajmi K et al. JAMA Netw Open. 2020;3(4):e203760.

A “favorable” lifestyle was associated with a reduced risk of breast cancer even among women at high genetic risk for the disease in a study of more than 90,000 women, researchers reported.

The findings suggest that, regardless of genetic risk, women may be able to reduce their risk of developing breast cancer by getting adequate levels of exercise; maintaining a healthy weight; and limiting or eliminating use of alcohol, oral contraceptives, and hormone replacement therapy.

Kawthar Al Ajmi, MSc, of the University of Manchester (England), and colleagues published these findings in JAMA Network Open.

With almost a quarter of breast cancers thought to be preventable in the United Kingdom, “it is important to understand the contribution of modifiable risk factors ... and how they affect or add to the inherited genetic factors,” the researchers wrote.

To that end, the team reviewed 91,217 white, postmenopausal women in the United Kingdom Biobank, an ongoing longitudinal study of the contribution of genetic, environmental, and lifestyle risk factors in disease. There were 2,728 women who developed breast cancer at a median follow-up of 10 years.

The investigators used a polygenic risk score to categorize subjects as low, intermediate, or high genetic risk. The score was constructed using 305 single-nucleotide variants.

Within each risk group, the researchers divided women by the presence or absence of five lifestyle factors previously associated with a lower risk of breast cancer: healthy weight, regular exercise, no use of hormone replacement therapy beyond 5 years, no oral contraceptive use, and alcohol intake no more than twice a week.

Women with four or more of these factors were deemed to have a favorable lifestyle. Women with two or three factors had an intermediate lifestyle, and women with fewer factors had an unfavorable lifestyle.
 

Results

The data showed an association between breast cancer and a body mass index of 25 or higher (relative risk, 1.14), no regular physical activity (RR, 1.12), alcohol intake at least three times per week (RR, 1.11), and use of hormone replacement therapy for 5 or more years (RR, 1.23). History of oral contraceptive use was not associated with breast cancer risk (RR, 1.02), but this factor remained a part of the lifestyle classification.

In the low genetic risk group, an intermediate lifestyle (hazard ratio, 1.40; 95% CI, 1.09-1.80) and an unfavorable lifestyle (HR, 1.63; 95% CI, 1.14-2.34) were both associated with a higher risk of breast cancer, compared with a favorable lifestyle.

In the intermediate genetic risk group, intermediate (HR, 1.37; 95% CI, 1.12-1.68) and unfavorable lifestyles (HR 1.94; 95% CI, 1.46-2.58) were again associated with higher breast cancer risk, compared with a favorable lifestyle .

Even in the high genetic risk group, intermediate (HR, 1.13; 95% CI, 0.98-1.31) and unfavorable lifestyles (HR, 1.39; 95% CI, 1.11-1.74) were associated with increased breast cancer risk. Results were adjusted for both age and family history.

In the end, “a healthier lifestyle ... appeared to be associated with a reduced level of risk for [breast cancer], even if the women were at higher genetic risk,” the researchers wrote. “Our findings suggest that women may be able to alter or reduce their risk of developing [breast cancer] by following healthier lifestyles,” regardless of genetic predisposition.
 

‘Surprising’ findings

It’s “surprising that these lifestyle changes lowered the risk of breast cancer,” said Charles Shapiro, MD, of the Icahn School of Medicine at Mount Sinai in New York, who was not involved in this study.

The study “requires replication,” he said. “On the other hand, these lifestyle changes promote overall health and certainly are associated with decreased risks of cardiovascular disease, the number one killer of women.”

“Patients always want to know what they can do above and beyond screening mammograms to reduce their risk of developing breast cancer,” said William Gradishar, MD, of Northwestern University in Chicago, who was not involved in the study.

“These data should empower patients that they can impact on their overall health and reduce the risk of developing breast cancer,” he said.

Among the study’s limitations, it’s unclear how the findings apply to nonwhite, nonpostmenopausal women, and the analysis did not differentiate between breast cancer subtypes.

In addition, although oral contraceptives have been linked to breast cancer in the past, there was no association in this study. Possible explanations could be that the investigators did not take into account duration of use, age of last use, and type or oral contraceptive used, they noted.

This research was funded by the National Institute for Health Research Manchester Biomedical Research Centre, the Alan Turing Institute, and a Cancer Research UK Integrated Cancer Epidemiology Programme grant. The investigators, Dr. Gradishar, and Dr. Shapiro have no relevant disclosures.

aotto@mdedge.com

SOURCE: Al Ajmi K et al. JAMA Netw Open. 2020;3(4):e203760.

The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.

The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.

In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.



The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.

Accelerated approval to treat solid tumors

The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.

The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).

The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.

Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.

The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.

The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.

Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
 

New option for recurrent or metastatic cSCC

Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.

The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.

The objective response rate was 34%, and the median duration of response was not reached.

Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.

The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.

The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.

In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.



The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.

Accelerated approval to treat solid tumors

The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.

The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).

The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.

Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.

The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.

The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.

Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
 

New option for recurrent or metastatic cSCC

Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.

The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.

The objective response rate was 34%, and the median duration of response was not reached.

Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.

The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.

The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.

In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.



The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.

Accelerated approval to treat solid tumors

The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.

The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).

The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.

Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.

The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.

The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.

Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
 

New option for recurrent or metastatic cSCC

Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.

The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.

The objective response rate was 34%, and the median duration of response was not reached.

Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.

The oral selective estrogen receptor degrader (SERD) LSZ102 plus either ribociclib or alpelisib shows manageable safety and encouraging clinical activity in heavily pretreated estrogen receptor (ER)–positive breast cancer patients who progressed after prior endocrine therapy, according to interim results of an open-label phase 1/1b study.

The effects seen in the study, which is the first to report on an oral SERD in combination with both CDK4/6 and PI3Ka inhibitors, occurred regardless of ESR1 and PIK3CA mutations, said Komal Jhaveri, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Jhaveri reported the results at the European Society of Medical Oncology: Breast Cancer virtual meeting.

The overall response rate (ORR) among 78 patients enrolled in an LSZ102 monotherapy arm (arm A) was 1.3%, and the progression-free survival (PFS) was 1.8 months. The clinical benefit rate (CBR) was 9.1%.

Among 76 patients enrolled in an LSZ102+ribociclib arm (arm B), the ORR was 15.8%, the PFS was 6.2 months, and the CBR was 35.5%.

Among the 39 patients enrolled in an LSZ102+alpelisib arm (arm C), the ORR was 5.4%, the PFS was 3.5 months, and the CBR was 18.9%.

After the data cutoff, one additional partial response (PR) was reported in arm C, Dr. Jhaveri said, noting that two of three confirmed responses were in known PIKC3A-mutant patients.

Study participants were aged 18 years and older with a confirmed diagnosis of ER-positive breast cancer and good performance status, as well as evidence of progression after endocrine therapy for metastatic disease or evidence of progression while on therapy or within 12 months from the end of adjuvant therapy.

“For all arms, prior fulvestrant, CDK46 inhibitor, or chemotherapy were allowed. For arm C, patients with or without PIK3C were eligible, and no prior treatment with PIK3, mTOR, or AKT inhibitors was allowed,” Dr. Jhaveri said.

Dosing in the LSZ102 monotherapy arm ranged from 200 to 900 mg. Arm B patients received LSZ102 at doses of 200-600 mg and ribociclib at doses of 200-600 mg. Both continuous ribociclib and 3 weeks on/1 week off dosing were evaluated. Arm C patients received LSZ102 at doses of 300-450 mg and alpelisib at 200-300 mg.

The recommended expansion doses were 450 mg daily of LSZ102 for arm A and 450 mg LSZ102 with 400 mg of daily ribociclib for arm B. For arm C, they were 300 mg LSZ102 with 250 mg of alpelisib daily.

Of note, two of three patients with a PR in arm C had received 300 mg LSZ102 and 300 mg alpelisib, Dr. Jhaveri said.

Arm A and arm B results were presented at the San Antonio Breast Cancer Symposium in 2018 and 2019, respectively. The current report updates those findings and presents arm C data for the first time, Dr. Jhaveri said.

LSZ102 was relatively well-tolerated as a single agent and in combination with ribociclib and alpelisib, according to Dr. Jhaveri. The most frequent adverse events were gastrointestinal toxicities, including nausea, vomiting, diarrhea, and decreased appetite, which occurred across all arms.

Neutropenia and aspartate aminotransferase abnormalities, including grade 3 cases, were reported in arm B and were most likely driven by the ribociclib, Dr. Jhaveri said. Grade 3 hypoglycemia and skin rash commonly occurred in arm C, most likely driven by the alpelisib.

Five dose-limiting toxicities occurred in four patients in arm A, three occurred in two patients in arm B, and seven occurred in seven patients in arm C.

Paired biopsies collected at the time of screening and at day 15 of cycle 1 showed consistent down-regulation of ER protein levels across arms.

“No substantial dose-dependent down-regulation of the ER was observed with increasing doses of LSZ,” Dr. Jhaveri said.

Circulating tumor DNA (ctDNA) analysis showed that the dominant mutations across the arms were ESR1, PIK3CA, and TP53. These were not shown to correlate with response and were not enriched upon progression in patients with matched baseline and end-of-treatment samples, she noted.

An exploratory analysis, conducted in “a preliminary attempt to correlate clinical activity with specific mutations,” showed that, in arms B and C, respectively, ORR, CBR, and PFS weren’t correlated with the presence or absence of ESR1 and PIK3CA mutations, respectively, or the absence of detectable ctDNA from baseline samples, Dr. Jhaveri said.

“While numerically higher responses and better CBR were seen in patients with undetectable ctDNA at baseline, no statistically significant difference in any of these outcomes was observed in arms B and C,” she said.

In arm C, the numbers were small at the time of data cutoff, but incoming data suggest relatively enhanced activity of the LSZ102 plus alpelisib combination in PIKC3A-mutant patients, she noted.

“We know that inhibiting ER signaling is the mainstay of treatment for ER-positive breast cancer,” Dr. Jhaveri explained, adding that aromatase inhibitors, estrogen receptor modulators, and SERDs are important classes of antiestrogenic agents, but fulvestrant is the only approved SERD. These are effective, but many patients develop resistance, she said.

“Proposed mechanisms for endocrine resistance include activation of the cell-cycle and cell-survival signaling pathways, or of the PI3K-AKT-mTOR pathway,” Dr. Jhaveri said. “To that end, ribociclib, a CDK46 inhibitor plus fulvestrant improved survival compared to fulvestrant alone in patients with ER-positive metastatic breast cancer.”

More recently, the PI3K inhibitor alpelisib plus fulvestrant also nearly doubled PFS vs. fulvestrant alone in PIKC3A-mutant, ER-positive metastatic breast cancer, which led to the approval of the combination in the United States.

Another mechanism of endocrine resistance includes acquisition of activating mutations in the estrogen receptor gene itself that allow tumors to survive and proliferate without depending on estrogen.

EGFR mutations appear to predict resistance to aromatase inhibitor therapies, but not outcomes in patients treated with fulvestrant. However, fulvestrant, which is delivered by intramuscular injection, has its own limitations, Dr. Jhaveri said.

“LSZ102 is a novel SERD that could achieve higher exposure than fulvestrant, leading to enhanced efficacy,” she said, noting that it was shown in preclinical models to have activity and to be synergistic in combination with ribociclib and alpelisib, forming the basis for the current study.

Invited discussant, Saverio Cinieri, MD, of Ospedale Antonio Perrino, Brindisi, Italy, said the study “elegantly demonstrated that estrogen receptor protein is down-regulated by LSZ102; [that] the genomic landscape of heavily pretreated patients is dominated by mutations in ESR1, PIK3CA, and TP53; [that] common mutations do not correlate with response and are not enriched on progression; [and that] ctDNA analysis at baseline shows similar outcomes with LSZ plus ribociclib or alpelisib, regardless of mutational status.”

LSZ102 is one of four new-generation SERDs in early-phase studies, he said, concluding that “in the COVID-19 era, the use of oral therapies will be even more necessary to limit access to the hospital.”

Dr. Cinieri also said that overcoming the limitations “of a molecule like the intramuscularly administered fulvestrant goes in this direction,” and that “the clinical efficacy and the biomolecular profile of LSZ102 seems to be able to meet these real needs.”

This study was funded by Novartis. Dr. Jhaveri reported advisory and consultancy roles and/or research grants or other funding to her institution from Novartis, ADC Therapeutics, Pfizer, and numerous other pharmaceutical and biotechnology companies. Dr. Cinieri reported relationships with Lily Oncology, Pfizer, Roche, AstraZeneca, Amgen, Novartis, including honoraria, grant and research support to his institution, advisory board participation, and scientific meeting support.

sworcester@mdedge.com

SOURCE: Jhaveri K et al. ESMO Breast Cancer, Abstract LBA1.

The oral selective estrogen receptor degrader (SERD) LSZ102 plus either ribociclib or alpelisib shows manageable safety and encouraging clinical activity in heavily pretreated estrogen receptor (ER)–positive breast cancer patients who progressed after prior endocrine therapy, according to interim results of an open-label phase 1/1b study.

The effects seen in the study, which is the first to report on an oral SERD in combination with both CDK4/6 and PI3Ka inhibitors, occurred regardless of ESR1 and PIK3CA mutations, said Komal Jhaveri, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Jhaveri reported the results at the European Society of Medical Oncology: Breast Cancer virtual meeting.

The overall response rate (ORR) among 78 patients enrolled in an LSZ102 monotherapy arm (arm A) was 1.3%, and the progression-free survival (PFS) was 1.8 months. The clinical benefit rate (CBR) was 9.1%.

Among 76 patients enrolled in an LSZ102+ribociclib arm (arm B), the ORR was 15.8%, the PFS was 6.2 months, and the CBR was 35.5%.

Among the 39 patients enrolled in an LSZ102+alpelisib arm (arm C), the ORR was 5.4%, the PFS was 3.5 months, and the CBR was 18.9%.

After the data cutoff, one additional partial response (PR) was reported in arm C, Dr. Jhaveri said, noting that two of three confirmed responses were in known PIKC3A-mutant patients.

Study participants were aged 18 years and older with a confirmed diagnosis of ER-positive breast cancer and good performance status, as well as evidence of progression after endocrine therapy for metastatic disease or evidence of progression while on therapy or within 12 months from the end of adjuvant therapy.

“For all arms, prior fulvestrant, CDK46 inhibitor, or chemotherapy were allowed. For arm C, patients with or without PIK3C were eligible, and no prior treatment with PIK3, mTOR, or AKT inhibitors was allowed,” Dr. Jhaveri said.

Dosing in the LSZ102 monotherapy arm ranged from 200 to 900 mg. Arm B patients received LSZ102 at doses of 200-600 mg and ribociclib at doses of 200-600 mg. Both continuous ribociclib and 3 weeks on/1 week off dosing were evaluated. Arm C patients received LSZ102 at doses of 300-450 mg and alpelisib at 200-300 mg.

The recommended expansion doses were 450 mg daily of LSZ102 for arm A and 450 mg LSZ102 with 400 mg of daily ribociclib for arm B. For arm C, they were 300 mg LSZ102 with 250 mg of alpelisib daily.

Of note, two of three patients with a PR in arm C had received 300 mg LSZ102 and 300 mg alpelisib, Dr. Jhaveri said.

Arm A and arm B results were presented at the San Antonio Breast Cancer Symposium in 2018 and 2019, respectively. The current report updates those findings and presents arm C data for the first time, Dr. Jhaveri said.

LSZ102 was relatively well-tolerated as a single agent and in combination with ribociclib and alpelisib, according to Dr. Jhaveri. The most frequent adverse events were gastrointestinal toxicities, including nausea, vomiting, diarrhea, and decreased appetite, which occurred across all arms.

Neutropenia and aspartate aminotransferase abnormalities, including grade 3 cases, were reported in arm B and were most likely driven by the ribociclib, Dr. Jhaveri said. Grade 3 hypoglycemia and skin rash commonly occurred in arm C, most likely driven by the alpelisib.

Five dose-limiting toxicities occurred in four patients in arm A, three occurred in two patients in arm B, and seven occurred in seven patients in arm C.

Paired biopsies collected at the time of screening and at day 15 of cycle 1 showed consistent down-regulation of ER protein levels across arms.

“No substantial dose-dependent down-regulation of the ER was observed with increasing doses of LSZ,” Dr. Jhaveri said.

Circulating tumor DNA (ctDNA) analysis showed that the dominant mutations across the arms were ESR1, PIK3CA, and TP53. These were not shown to correlate with response and were not enriched upon progression in patients with matched baseline and end-of-treatment samples, she noted.

An exploratory analysis, conducted in “a preliminary attempt to correlate clinical activity with specific mutations,” showed that, in arms B and C, respectively, ORR, CBR, and PFS weren’t correlated with the presence or absence of ESR1 and PIK3CA mutations, respectively, or the absence of detectable ctDNA from baseline samples, Dr. Jhaveri said.

“While numerically higher responses and better CBR were seen in patients with undetectable ctDNA at baseline, no statistically significant difference in any of these outcomes was observed in arms B and C,” she said.

In arm C, the numbers were small at the time of data cutoff, but incoming data suggest relatively enhanced activity of the LSZ102 plus alpelisib combination in PIKC3A-mutant patients, she noted.

“We know that inhibiting ER signaling is the mainstay of treatment for ER-positive breast cancer,” Dr. Jhaveri explained, adding that aromatase inhibitors, estrogen receptor modulators, and SERDs are important classes of antiestrogenic agents, but fulvestrant is the only approved SERD. These are effective, but many patients develop resistance, she said.

“Proposed mechanisms for endocrine resistance include activation of the cell-cycle and cell-survival signaling pathways, or of the PI3K-AKT-mTOR pathway,” Dr. Jhaveri said. “To that end, ribociclib, a CDK46 inhibitor plus fulvestrant improved survival compared to fulvestrant alone in patients with ER-positive metastatic breast cancer.”

More recently, the PI3K inhibitor alpelisib plus fulvestrant also nearly doubled PFS vs. fulvestrant alone in PIKC3A-mutant, ER-positive metastatic breast cancer, which led to the approval of the combination in the United States.

Another mechanism of endocrine resistance includes acquisition of activating mutations in the estrogen receptor gene itself that allow tumors to survive and proliferate without depending on estrogen.

EGFR mutations appear to predict resistance to aromatase inhibitor therapies, but not outcomes in patients treated with fulvestrant. However, fulvestrant, which is delivered by intramuscular injection, has its own limitations, Dr. Jhaveri said.

“LSZ102 is a novel SERD that could achieve higher exposure than fulvestrant, leading to enhanced efficacy,” she said, noting that it was shown in preclinical models to have activity and to be synergistic in combination with ribociclib and alpelisib, forming the basis for the current study.

Invited discussant, Saverio Cinieri, MD, of Ospedale Antonio Perrino, Brindisi, Italy, said the study “elegantly demonstrated that estrogen receptor protein is down-regulated by LSZ102; [that] the genomic landscape of heavily pretreated patients is dominated by mutations in ESR1, PIK3CA, and TP53; [that] common mutations do not correlate with response and are not enriched on progression; [and that] ctDNA analysis at baseline shows similar outcomes with LSZ plus ribociclib or alpelisib, regardless of mutational status.”

LSZ102 is one of four new-generation SERDs in early-phase studies, he said, concluding that “in the COVID-19 era, the use of oral therapies will be even more necessary to limit access to the hospital.”

Dr. Cinieri also said that overcoming the limitations “of a molecule like the intramuscularly administered fulvestrant goes in this direction,” and that “the clinical efficacy and the biomolecular profile of LSZ102 seems to be able to meet these real needs.”

This study was funded by Novartis. Dr. Jhaveri reported advisory and consultancy roles and/or research grants or other funding to her institution from Novartis, ADC Therapeutics, Pfizer, and numerous other pharmaceutical and biotechnology companies. Dr. Cinieri reported relationships with Lily Oncology, Pfizer, Roche, AstraZeneca, Amgen, Novartis, including honoraria, grant and research support to his institution, advisory board participation, and scientific meeting support.

sworcester@mdedge.com

SOURCE: Jhaveri K et al. ESMO Breast Cancer, Abstract LBA1.

The oral selective estrogen receptor degrader (SERD) LSZ102 plus either ribociclib or alpelisib shows manageable safety and encouraging clinical activity in heavily pretreated estrogen receptor (ER)–positive breast cancer patients who progressed after prior endocrine therapy, according to interim results of an open-label phase 1/1b study.

The effects seen in the study, which is the first to report on an oral SERD in combination with both CDK4/6 and PI3Ka inhibitors, occurred regardless of ESR1 and PIK3CA mutations, said Komal Jhaveri, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Jhaveri reported the results at the European Society of Medical Oncology: Breast Cancer virtual meeting.

The overall response rate (ORR) among 78 patients enrolled in an LSZ102 monotherapy arm (arm A) was 1.3%, and the progression-free survival (PFS) was 1.8 months. The clinical benefit rate (CBR) was 9.1%.

Among 76 patients enrolled in an LSZ102+ribociclib arm (arm B), the ORR was 15.8%, the PFS was 6.2 months, and the CBR was 35.5%.

Among the 39 patients enrolled in an LSZ102+alpelisib arm (arm C), the ORR was 5.4%, the PFS was 3.5 months, and the CBR was 18.9%.

After the data cutoff, one additional partial response (PR) was reported in arm C, Dr. Jhaveri said, noting that two of three confirmed responses were in known PIKC3A-mutant patients.

Study participants were aged 18 years and older with a confirmed diagnosis of ER-positive breast cancer and good performance status, as well as evidence of progression after endocrine therapy for metastatic disease or evidence of progression while on therapy or within 12 months from the end of adjuvant therapy.

“For all arms, prior fulvestrant, CDK46 inhibitor, or chemotherapy were allowed. For arm C, patients with or without PIK3C were eligible, and no prior treatment with PIK3, mTOR, or AKT inhibitors was allowed,” Dr. Jhaveri said.

Dosing in the LSZ102 monotherapy arm ranged from 200 to 900 mg. Arm B patients received LSZ102 at doses of 200-600 mg and ribociclib at doses of 200-600 mg. Both continuous ribociclib and 3 weeks on/1 week off dosing were evaluated. Arm C patients received LSZ102 at doses of 300-450 mg and alpelisib at 200-300 mg.

The recommended expansion doses were 450 mg daily of LSZ102 for arm A and 450 mg LSZ102 with 400 mg of daily ribociclib for arm B. For arm C, they were 300 mg LSZ102 with 250 mg of alpelisib daily.

Of note, two of three patients with a PR in arm C had received 300 mg LSZ102 and 300 mg alpelisib, Dr. Jhaveri said.

Arm A and arm B results were presented at the San Antonio Breast Cancer Symposium in 2018 and 2019, respectively. The current report updates those findings and presents arm C data for the first time, Dr. Jhaveri said.

LSZ102 was relatively well-tolerated as a single agent and in combination with ribociclib and alpelisib, according to Dr. Jhaveri. The most frequent adverse events were gastrointestinal toxicities, including nausea, vomiting, diarrhea, and decreased appetite, which occurred across all arms.

Neutropenia and aspartate aminotransferase abnormalities, including grade 3 cases, were reported in arm B and were most likely driven by the ribociclib, Dr. Jhaveri said. Grade 3 hypoglycemia and skin rash commonly occurred in arm C, most likely driven by the alpelisib.

Five dose-limiting toxicities occurred in four patients in arm A, three occurred in two patients in arm B, and seven occurred in seven patients in arm C.

Paired biopsies collected at the time of screening and at day 15 of cycle 1 showed consistent down-regulation of ER protein levels across arms.

“No substantial dose-dependent down-regulation of the ER was observed with increasing doses of LSZ,” Dr. Jhaveri said.

Circulating tumor DNA (ctDNA) analysis showed that the dominant mutations across the arms were ESR1, PIK3CA, and TP53. These were not shown to correlate with response and were not enriched upon progression in patients with matched baseline and end-of-treatment samples, she noted.

An exploratory analysis, conducted in “a preliminary attempt to correlate clinical activity with specific mutations,” showed that, in arms B and C, respectively, ORR, CBR, and PFS weren’t correlated with the presence or absence of ESR1 and PIK3CA mutations, respectively, or the absence of detectable ctDNA from baseline samples, Dr. Jhaveri said.

“While numerically higher responses and better CBR were seen in patients with undetectable ctDNA at baseline, no statistically significant difference in any of these outcomes was observed in arms B and C,” she said.

In arm C, the numbers were small at the time of data cutoff, but incoming data suggest relatively enhanced activity of the LSZ102 plus alpelisib combination in PIKC3A-mutant patients, she noted.

“We know that inhibiting ER signaling is the mainstay of treatment for ER-positive breast cancer,” Dr. Jhaveri explained, adding that aromatase inhibitors, estrogen receptor modulators, and SERDs are important classes of antiestrogenic agents, but fulvestrant is the only approved SERD. These are effective, but many patients develop resistance, she said.

“Proposed mechanisms for endocrine resistance include activation of the cell-cycle and cell-survival signaling pathways, or of the PI3K-AKT-mTOR pathway,” Dr. Jhaveri said. “To that end, ribociclib, a CDK46 inhibitor plus fulvestrant improved survival compared to fulvestrant alone in patients with ER-positive metastatic breast cancer.”

More recently, the PI3K inhibitor alpelisib plus fulvestrant also nearly doubled PFS vs. fulvestrant alone in PIKC3A-mutant, ER-positive metastatic breast cancer, which led to the approval of the combination in the United States.

Another mechanism of endocrine resistance includes acquisition of activating mutations in the estrogen receptor gene itself that allow tumors to survive and proliferate without depending on estrogen.

EGFR mutations appear to predict resistance to aromatase inhibitor therapies, but not outcomes in patients treated with fulvestrant. However, fulvestrant, which is delivered by intramuscular injection, has its own limitations, Dr. Jhaveri said.

“LSZ102 is a novel SERD that could achieve higher exposure than fulvestrant, leading to enhanced efficacy,” she said, noting that it was shown in preclinical models to have activity and to be synergistic in combination with ribociclib and alpelisib, forming the basis for the current study.

Invited discussant, Saverio Cinieri, MD, of Ospedale Antonio Perrino, Brindisi, Italy, said the study “elegantly demonstrated that estrogen receptor protein is down-regulated by LSZ102; [that] the genomic landscape of heavily pretreated patients is dominated by mutations in ESR1, PIK3CA, and TP53; [that] common mutations do not correlate with response and are not enriched on progression; [and that] ctDNA analysis at baseline shows similar outcomes with LSZ plus ribociclib or alpelisib, regardless of mutational status.”

LSZ102 is one of four new-generation SERDs in early-phase studies, he said, concluding that “in the COVID-19 era, the use of oral therapies will be even more necessary to limit access to the hospital.”

Dr. Cinieri also said that overcoming the limitations “of a molecule like the intramuscularly administered fulvestrant goes in this direction,” and that “the clinical efficacy and the biomolecular profile of LSZ102 seems to be able to meet these real needs.”

This study was funded by Novartis. Dr. Jhaveri reported advisory and consultancy roles and/or research grants or other funding to her institution from Novartis, ADC Therapeutics, Pfizer, and numerous other pharmaceutical and biotechnology companies. Dr. Cinieri reported relationships with Lily Oncology, Pfizer, Roche, AstraZeneca, Amgen, Novartis, including honoraria, grant and research support to his institution, advisory board participation, and scientific meeting support.

sworcester@mdedge.com

SOURCE: Jhaveri K et al. ESMO Breast Cancer, Abstract LBA1.

The Food and Drug Administration approved a combination of pertuzumab (Perjeta, Genentech/Roche), trastuzumab (Herceptin, Genentech/Roche) and hyaluronidase (Phesgo, Genentech/Roche) that is administered subcutaneously – rather than intravenously – for the treatment of early and metastatic HER2-positive breast cancers.

Phesgo is initially used in combination with chemotherapy at an infusion center but could continue to be administered in a patient’s home by a qualified health care professional once chemotherapy is complete, according to the FDA.

Administration takes approximately 8 minutes for the initial loading dose and approximately 5 minutes for maintenance doses, according to a Genentech press statement. This compares favorably with the 150 minutes needed for the combined loading dose of intravenous pertuzumab and trastuzumab, and the 60-150 minutes for intravenous maintenance infusions, the company said.

“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, Phesgo offers an outpatient option for patients to receive trastuzumab and pertuzumab,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in an agency press release.

“The fixed-dose combination of trastuzumab and pertuzumab offers a simpler, faster, and easier treatment experience for patients with HER2-positive breast cancer,” said Antoinette Tan, MD, MHSc, chief of breast medical oncology at Levine Cancer Institute, Charlotte, N.C., in the company statement.

Dr. Tan also said that home administration “can be advantageous for patients and infusion centers.”

However, in April, the Community Oncology Alliance strenuously objected to this type of treatment in a patient’s home, as reported by Medscape Medical News.

The group, which represents U.S. community-based practices, said it “fundamentally opposes home infusion of chemotherapy, cancer immunotherapy, and cancer treatment supportive drugs because of serious patient safety concerns.”

The FDA’s approval was based on the results of the pivotal phase 3 FeDeriCa trial, a noninferiority study in patients with HER2-positive early breast cancer, which demonstrated that the new product had comparable efficacy and safety as intravenous pertuzumab and intravenous trastuzumab.

In terms of efficacy, the subcutaneous product demonstrated noninferior plasma levels of pertuzumab, which was the primary endpoint, when compared with IV administration of pertuzumab.

Safety was comparable between the two approaches, with no new safety signals using the subcutaneous delivery method, including no “meaningful difference” in cardiac toxicity, according to Genentech. However, there were more administration-related reactions with the new product. The most common adverse events in both groups were alopecia, nausea, diarrhea, and anemia.

The new product uses a drug delivery technology (Enhanze, Halozyme Therapeutics) that employs a proprietary enzyme that temporarily degrades hyaluronan, a glycosaminoglycan or chain of natural sugars in the body, to facilitate the dispersion and absorption of injected therapeutic drugs, according to Genentech.

In May, at the European Society for Medical Oncology Breast Cancer Virtual Meeting 2020, investigators of the phase 2 PHranceSCa study reported that “more than 80%” of patients preferred subcutaneous to intravenous administration of pertuzumab and trastuzumab.

This article first appeared on Medscape.com.

The Food and Drug Administration approved a combination of pertuzumab (Perjeta, Genentech/Roche), trastuzumab (Herceptin, Genentech/Roche) and hyaluronidase (Phesgo, Genentech/Roche) that is administered subcutaneously – rather than intravenously – for the treatment of early and metastatic HER2-positive breast cancers.

Phesgo is initially used in combination with chemotherapy at an infusion center but could continue to be administered in a patient’s home by a qualified health care professional once chemotherapy is complete, according to the FDA.

Administration takes approximately 8 minutes for the initial loading dose and approximately 5 minutes for maintenance doses, according to a Genentech press statement. This compares favorably with the 150 minutes needed for the combined loading dose of intravenous pertuzumab and trastuzumab, and the 60-150 minutes for intravenous maintenance infusions, the company said.

“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, Phesgo offers an outpatient option for patients to receive trastuzumab and pertuzumab,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in an agency press release.

“The fixed-dose combination of trastuzumab and pertuzumab offers a simpler, faster, and easier treatment experience for patients with HER2-positive breast cancer,” said Antoinette Tan, MD, MHSc, chief of breast medical oncology at Levine Cancer Institute, Charlotte, N.C., in the company statement.

Dr. Tan also said that home administration “can be advantageous for patients and infusion centers.”

However, in April, the Community Oncology Alliance strenuously objected to this type of treatment in a patient’s home, as reported by Medscape Medical News.

The group, which represents U.S. community-based practices, said it “fundamentally opposes home infusion of chemotherapy, cancer immunotherapy, and cancer treatment supportive drugs because of serious patient safety concerns.”

The FDA’s approval was based on the results of the pivotal phase 3 FeDeriCa trial, a noninferiority study in patients with HER2-positive early breast cancer, which demonstrated that the new product had comparable efficacy and safety as intravenous pertuzumab and intravenous trastuzumab.

In terms of efficacy, the subcutaneous product demonstrated noninferior plasma levels of pertuzumab, which was the primary endpoint, when compared with IV administration of pertuzumab.

Safety was comparable between the two approaches, with no new safety signals using the subcutaneous delivery method, including no “meaningful difference” in cardiac toxicity, according to Genentech. However, there were more administration-related reactions with the new product. The most common adverse events in both groups were alopecia, nausea, diarrhea, and anemia.

The new product uses a drug delivery technology (Enhanze, Halozyme Therapeutics) that employs a proprietary enzyme that temporarily degrades hyaluronan, a glycosaminoglycan or chain of natural sugars in the body, to facilitate the dispersion and absorption of injected therapeutic drugs, according to Genentech.

In May, at the European Society for Medical Oncology Breast Cancer Virtual Meeting 2020, investigators of the phase 2 PHranceSCa study reported that “more than 80%” of patients preferred subcutaneous to intravenous administration of pertuzumab and trastuzumab.

This article first appeared on Medscape.com.

The Food and Drug Administration approved a combination of pertuzumab (Perjeta, Genentech/Roche), trastuzumab (Herceptin, Genentech/Roche) and hyaluronidase (Phesgo, Genentech/Roche) that is administered subcutaneously – rather than intravenously – for the treatment of early and metastatic HER2-positive breast cancers.

Phesgo is initially used in combination with chemotherapy at an infusion center but could continue to be administered in a patient’s home by a qualified health care professional once chemotherapy is complete, according to the FDA.

Administration takes approximately 8 minutes for the initial loading dose and approximately 5 minutes for maintenance doses, according to a Genentech press statement. This compares favorably with the 150 minutes needed for the combined loading dose of intravenous pertuzumab and trastuzumab, and the 60-150 minutes for intravenous maintenance infusions, the company said.

“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, Phesgo offers an outpatient option for patients to receive trastuzumab and pertuzumab,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in an agency press release.

“The fixed-dose combination of trastuzumab and pertuzumab offers a simpler, faster, and easier treatment experience for patients with HER2-positive breast cancer,” said Antoinette Tan, MD, MHSc, chief of breast medical oncology at Levine Cancer Institute, Charlotte, N.C., in the company statement.

Dr. Tan also said that home administration “can be advantageous for patients and infusion centers.”

However, in April, the Community Oncology Alliance strenuously objected to this type of treatment in a patient’s home, as reported by Medscape Medical News.

The group, which represents U.S. community-based practices, said it “fundamentally opposes home infusion of chemotherapy, cancer immunotherapy, and cancer treatment supportive drugs because of serious patient safety concerns.”

The FDA’s approval was based on the results of the pivotal phase 3 FeDeriCa trial, a noninferiority study in patients with HER2-positive early breast cancer, which demonstrated that the new product had comparable efficacy and safety as intravenous pertuzumab and intravenous trastuzumab.

In terms of efficacy, the subcutaneous product demonstrated noninferior plasma levels of pertuzumab, which was the primary endpoint, when compared with IV administration of pertuzumab.

Safety was comparable between the two approaches, with no new safety signals using the subcutaneous delivery method, including no “meaningful difference” in cardiac toxicity, according to Genentech. However, there were more administration-related reactions with the new product. The most common adverse events in both groups were alopecia, nausea, diarrhea, and anemia.

The new product uses a drug delivery technology (Enhanze, Halozyme Therapeutics) that employs a proprietary enzyme that temporarily degrades hyaluronan, a glycosaminoglycan or chain of natural sugars in the body, to facilitate the dispersion and absorption of injected therapeutic drugs, according to Genentech.

In May, at the European Society for Medical Oncology Breast Cancer Virtual Meeting 2020, investigators of the phase 2 PHranceSCa study reported that “more than 80%” of patients preferred subcutaneous to intravenous administration of pertuzumab and trastuzumab.

This article first appeared on Medscape.com.

Combining a personalized cancer vaccine with an immune checkpoint inhibitor induced neoantigen-specific immune responses in most patients with advanced solid tumors in a phase 1b study.

Only two clinical responses were seen in this early investigation of the vaccine, RO7198457, combined with the PD-L1 inhibitor atezolizumab. However, T-cell responses were observed in about three-quarters of the patients evaluated, according to study investigator Juanita Lopez, MB BChir, PhD.

Those immune responses, coupled with preliminary evidence of infiltration of RO7198457-stimulated T cells into tumors, suggest the viability of this individualized anticancer strategy, according to Dr. Lopez, a consultant medical oncologist at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London.

“Failure of T-cell priming is a major cause of lack of response to immune checkpoint inhibitors,” Dr. Lopez said in an interview. “We hoped that, by eliciting a tumor-specific T-cell response, we would be able to overcome this.”

Preclinical data suggested the combination of vaccine and immune checkpoint inhibitors improved outcomes, which prompted the current study, added Dr. Lopez, who presented results from this study at the American Association for Cancer Research virtual meeting II.

Dr. Lopez noted that mutated neoantigens are recognized as foreign and have been shown to induce stronger T-cell responses, compared with shared antigens, likely because of a lack of central tolerance.

“Most of these mutated neoantigens are not shared between the patients, and therefore, targeted neoantigen-specific therapy requires an individualized approach,” she explained.

RO7198457 is manufactured on a per-patient basis and includes as many as 20 tumor-specific neoepitopes.
 

Study details

Dr. Lopez presented results from dose-escalation and expansion cohorts of the study, which included 142 patients with advanced solid tumors. The patients had colorectal, skin, kidney, lung, urothelial, breast, gynecologic, and head and neck cancers.

Most patients had low or no PD-L1 expression, and nearly 40% had received prior treatment with a checkpoint inhibitor.

Patients received nine doses of RO7198457 at 25-50 mcg during the 12-week induction stage. They then received RO7198457 every eight cycles until disease progression. Patients received atezolizumab at 1,200 mg on day 1 of each 21-day cycle.

Induction of proinflammatory cytokines was observed at each dose tested, and ex vivo T-cell responses were noted in 46 of 63 patients evaluated, or 73%.

T-cell receptors specific to RO7198457 were present posttreatment in a patient with rectal cancer, providing some preliminary evidence suggesting infiltration of RO7198457-stimulated T cells in the tumor, Dr. Lopez said.

There were two clinical responses. A patient with rectal cancer had a complete response, and a patient with triple-negative breast cancer had a partial response.

The combination of RO7198457 with atezolizumab was generally well tolerated, and the maximum tolerated dose was not reached, Dr. Lopez said. Most adverse events were grade 1/2, and immune-mediated adverse events were rare.
 

Implications and next steps

This study furthers earlier observations from neoantigen vaccine studies by linking dosing of the vaccine to dosing with immune checkpoint inhibitor, rather than giving the vaccine in the period leading up to immune checkpoint inhibitor administration, according to former AACR President Elaine R. Mardis, PhD, of Nationwide Children’s Hospital and The Ohio State University College of Medicine, both in Columbus.

That said, the implications for clinical practice remain unclear, according to Dr. Mardis.

“This combination did elicit an immune response that was highly specific for the neoantigen vaccine, but most patients did not receive a clinical benefit of disease response,” Dr. Mardis said in an interview. “This tells us the combination approach used was, overall, not quite right, and we need to continue to innovate in this area.”

The low clinical response rate in the study was likely caused in part by the fact that patients had very advanced disease and were heavily pretreated, according to Dr. Lopez

Randomized phase 2 studies of RO7198457 are now underway, Dr. Lopez said. One is a study of RO7198457 plus atezolizumab as adjuvant treatment for non–small cell lung cancer (NCT04267237). Another is testing RO7198457 in combination with pembrolizumab as first-line treatment for melanoma (NCT03815058).

The current study was funded by Genentech and BioNTech. Dr. Lopez reported disclosures related to Roche/Genentech, Basilea Pharmaceutica, and Genmab. Dr. Mardis reported disclosures related to Quiagen NV, PACT Pharma, Kiadis Pharma NV, and Interpreta.

SOURCE: Lopez J et al. AACR 2020, Abstract CT301.

Combining a personalized cancer vaccine with an immune checkpoint inhibitor induced neoantigen-specific immune responses in most patients with advanced solid tumors in a phase 1b study.

Only two clinical responses were seen in this early investigation of the vaccine, RO7198457, combined with the PD-L1 inhibitor atezolizumab. However, T-cell responses were observed in about three-quarters of the patients evaluated, according to study investigator Juanita Lopez, MB BChir, PhD.

Those immune responses, coupled with preliminary evidence of infiltration of RO7198457-stimulated T cells into tumors, suggest the viability of this individualized anticancer strategy, according to Dr. Lopez, a consultant medical oncologist at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London.

“Failure of T-cell priming is a major cause of lack of response to immune checkpoint inhibitors,” Dr. Lopez said in an interview. “We hoped that, by eliciting a tumor-specific T-cell response, we would be able to overcome this.”

Preclinical data suggested the combination of vaccine and immune checkpoint inhibitors improved outcomes, which prompted the current study, added Dr. Lopez, who presented results from this study at the American Association for Cancer Research virtual meeting II.

Dr. Lopez noted that mutated neoantigens are recognized as foreign and have been shown to induce stronger T-cell responses, compared with shared antigens, likely because of a lack of central tolerance.

“Most of these mutated neoantigens are not shared between the patients, and therefore, targeted neoantigen-specific therapy requires an individualized approach,” she explained.

RO7198457 is manufactured on a per-patient basis and includes as many as 20 tumor-specific neoepitopes.
 

Study details

Dr. Lopez presented results from dose-escalation and expansion cohorts of the study, which included 142 patients with advanced solid tumors. The patients had colorectal, skin, kidney, lung, urothelial, breast, gynecologic, and head and neck cancers.

Most patients had low or no PD-L1 expression, and nearly 40% had received prior treatment with a checkpoint inhibitor.

Patients received nine doses of RO7198457 at 25-50 mcg during the 12-week induction stage. They then received RO7198457 every eight cycles until disease progression. Patients received atezolizumab at 1,200 mg on day 1 of each 21-day cycle.

Induction of proinflammatory cytokines was observed at each dose tested, and ex vivo T-cell responses were noted in 46 of 63 patients evaluated, or 73%.

T-cell receptors specific to RO7198457 were present posttreatment in a patient with rectal cancer, providing some preliminary evidence suggesting infiltration of RO7198457-stimulated T cells in the tumor, Dr. Lopez said.

There were two clinical responses. A patient with rectal cancer had a complete response, and a patient with triple-negative breast cancer had a partial response.

The combination of RO7198457 with atezolizumab was generally well tolerated, and the maximum tolerated dose was not reached, Dr. Lopez said. Most adverse events were grade 1/2, and immune-mediated adverse events were rare.
 

Implications and next steps

This study furthers earlier observations from neoantigen vaccine studies by linking dosing of the vaccine to dosing with immune checkpoint inhibitor, rather than giving the vaccine in the period leading up to immune checkpoint inhibitor administration, according to former AACR President Elaine R. Mardis, PhD, of Nationwide Children’s Hospital and The Ohio State University College of Medicine, both in Columbus.

That said, the implications for clinical practice remain unclear, according to Dr. Mardis.

“This combination did elicit an immune response that was highly specific for the neoantigen vaccine, but most patients did not receive a clinical benefit of disease response,” Dr. Mardis said in an interview. “This tells us the combination approach used was, overall, not quite right, and we need to continue to innovate in this area.”

The low clinical response rate in the study was likely caused in part by the fact that patients had very advanced disease and were heavily pretreated, according to Dr. Lopez

Randomized phase 2 studies of RO7198457 are now underway, Dr. Lopez said. One is a study of RO7198457 plus atezolizumab as adjuvant treatment for non–small cell lung cancer (NCT04267237). Another is testing RO7198457 in combination with pembrolizumab as first-line treatment for melanoma (NCT03815058).

The current study was funded by Genentech and BioNTech. Dr. Lopez reported disclosures related to Roche/Genentech, Basilea Pharmaceutica, and Genmab. Dr. Mardis reported disclosures related to Quiagen NV, PACT Pharma, Kiadis Pharma NV, and Interpreta.

SOURCE: Lopez J et al. AACR 2020, Abstract CT301.

Combining a personalized cancer vaccine with an immune checkpoint inhibitor induced neoantigen-specific immune responses in most patients with advanced solid tumors in a phase 1b study.

Only two clinical responses were seen in this early investigation of the vaccine, RO7198457, combined with the PD-L1 inhibitor atezolizumab. However, T-cell responses were observed in about three-quarters of the patients evaluated, according to study investigator Juanita Lopez, MB BChir, PhD.

Those immune responses, coupled with preliminary evidence of infiltration of RO7198457-stimulated T cells into tumors, suggest the viability of this individualized anticancer strategy, according to Dr. Lopez, a consultant medical oncologist at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London.

“Failure of T-cell priming is a major cause of lack of response to immune checkpoint inhibitors,” Dr. Lopez said in an interview. “We hoped that, by eliciting a tumor-specific T-cell response, we would be able to overcome this.”

Preclinical data suggested the combination of vaccine and immune checkpoint inhibitors improved outcomes, which prompted the current study, added Dr. Lopez, who presented results from this study at the American Association for Cancer Research virtual meeting II.

Dr. Lopez noted that mutated neoantigens are recognized as foreign and have been shown to induce stronger T-cell responses, compared with shared antigens, likely because of a lack of central tolerance.

“Most of these mutated neoantigens are not shared between the patients, and therefore, targeted neoantigen-specific therapy requires an individualized approach,” she explained.

RO7198457 is manufactured on a per-patient basis and includes as many as 20 tumor-specific neoepitopes.
 

Study details

Dr. Lopez presented results from dose-escalation and expansion cohorts of the study, which included 142 patients with advanced solid tumors. The patients had colorectal, skin, kidney, lung, urothelial, breast, gynecologic, and head and neck cancers.

Most patients had low or no PD-L1 expression, and nearly 40% had received prior treatment with a checkpoint inhibitor.

Patients received nine doses of RO7198457 at 25-50 mcg during the 12-week induction stage. They then received RO7198457 every eight cycles until disease progression. Patients received atezolizumab at 1,200 mg on day 1 of each 21-day cycle.

Induction of proinflammatory cytokines was observed at each dose tested, and ex vivo T-cell responses were noted in 46 of 63 patients evaluated, or 73%.

T-cell receptors specific to RO7198457 were present posttreatment in a patient with rectal cancer, providing some preliminary evidence suggesting infiltration of RO7198457-stimulated T cells in the tumor, Dr. Lopez said.

There were two clinical responses. A patient with rectal cancer had a complete response, and a patient with triple-negative breast cancer had a partial response.

The combination of RO7198457 with atezolizumab was generally well tolerated, and the maximum tolerated dose was not reached, Dr. Lopez said. Most adverse events were grade 1/2, and immune-mediated adverse events were rare.
 

Implications and next steps

This study furthers earlier observations from neoantigen vaccine studies by linking dosing of the vaccine to dosing with immune checkpoint inhibitor, rather than giving the vaccine in the period leading up to immune checkpoint inhibitor administration, according to former AACR President Elaine R. Mardis, PhD, of Nationwide Children’s Hospital and The Ohio State University College of Medicine, both in Columbus.

That said, the implications for clinical practice remain unclear, according to Dr. Mardis.

“This combination did elicit an immune response that was highly specific for the neoantigen vaccine, but most patients did not receive a clinical benefit of disease response,” Dr. Mardis said in an interview. “This tells us the combination approach used was, overall, not quite right, and we need to continue to innovate in this area.”

The low clinical response rate in the study was likely caused in part by the fact that patients had very advanced disease and were heavily pretreated, according to Dr. Lopez

Randomized phase 2 studies of RO7198457 are now underway, Dr. Lopez said. One is a study of RO7198457 plus atezolizumab as adjuvant treatment for non–small cell lung cancer (NCT04267237). Another is testing RO7198457 in combination with pembrolizumab as first-line treatment for melanoma (NCT03815058).

The current study was funded by Genentech and BioNTech. Dr. Lopez reported disclosures related to Roche/Genentech, Basilea Pharmaceutica, and Genmab. Dr. Mardis reported disclosures related to Quiagen NV, PACT Pharma, Kiadis Pharma NV, and Interpreta.

SOURCE: Lopez J et al. AACR 2020, Abstract CT301.

A model created by the National Cancer Institute predicts that tens of thousands of excess cancer deaths will occur over the next decade as a result of missed screenings, delays in diagnosis, and reductions in oncology care caused by the COVID-19 pandemic.

“As director of NCI, I am deeply concerned about the potential impacts of delayed diagnoses and deferred or modified treatment plans on cancer incidence and mortality,” said Norman “Ned” Sharpless, MD.

“In the past 3 decades, we have seen steady and strong progress against death and suffering from cancer, thanks to improvements in prevention, screening, diagnosis, and treatment. I worry that the SARS-CoV-2 pandemic has put those decades of steady progress at risk and may precipitate reversals of these trends.”

In an editorial published June 19 in Science, Dr. Sharpless highlighted modeling performed by the NCI that predicts an excess of 10,000 deaths from breast and colorectal cancer over the next 10 years.

The number of excess deaths per year would peak in the next year or 2, likely sooner for colorectal than for breast cancer, but “for both cancer types, we believe the pandemic will influence cancer deaths for at least a decade.”

In an interview, Dr. Sharpless pointed out that this analysis is conservative because the researchers only evaluated two types of cancer. They chose breast and colorectal cancer because these are common cancers (accounting for about one-sixth of all cancers) with relatively high screening rates.

“We didn’t model other cancer types, but we have no reason to think that we’re not going to see the same thing with other types of malignancies,” he said. “That is a significant amount of excess mortality.”
 

Delayed diagnosis, modified therapy

One of the effects of the pandemic has been to cause delays in cancer diagnosis. “Routine screening has plummeted and is running at less than 90% in some systems,” Dr. Sharpless said.

“Most cancers are diagnosed when people experience symptoms and go see their doctors, and those symptomatic screening events are also not happening,” he continued. “Fear of contracting the coronavirus in health care settings has dissuaded people from visits.”

In some cases, a delay in diagnosis will allow the cancer to progress to a more advanced stage. “The earlier the diagnosis, the better, and if the stages are more advanced, patients will not do as well for virtually every kind of cancer,” he said.

In addition to delays in diagnosis, treatments are being postponed or modified for patients recently diagnosed with cancer. Because of delays and reductions in curative therapies, patients may be receiving less than optimal care.

“We are seeing a lot of nonstandard care,” said Dr. Sharpless. “All of these things add up to increased cancer morbidity and mortality.”

He also pointed out that the term “elective” is confusing and problematic. “It doesn’t mean that it’s not needed, just that it’s not an emergency and doesn’t need to be done today,” said Dr. Sharpless. “But if we’re talking about chemotherapy and surgery, we don’t think they can be delayed for too long – maybe a week, but not for several months.”

Dr. Sharpless feels that overall it is time for cancer care to resume as much as possible, because “ignoring cancer for too long is an untenable choice and may turn one public health crisis into another.”

“If we act now, we can make up for lost time,” he wrote in the editorial. “Clearly, postponing procedures and deferring care due to the pandemic was prudent at one time, but now that we have made it through the initial shock of the pandemic, I believe it is time to resume robust cancer care.”

Through their network of cancer centers, researchers with the NCI can develop innovative solutions that allow screening and treatment to move forward while maintaining safety. “We need to make patients feel safe, and we have to answer important questions quickly,” he said.
 

Impact of COVID-19 on cancer care

The COVID-19 pandemic has overwhelmed health care systems worldwide and has created major challenges for clinicians who are caring for patients with cancer.

As previously reported, hospitals reprioritized resources for an impending onslaught of COVID-19 patients. Services and procedures deemed to be nonessential were canceled or delayed, including surgeries and imaging.

In a survey conducted by the American Cancer Society Cancer Action Network, half of the 1219 respondents reported changes, delays, or disruptions to the care they were receiving. The services most frequently affected included in-person provider visits (50%), supportive services (20%), and imaging procedures to monitor tumor growth (20%).

In addition, 8% reported that their treatment, including chemotherapy and immunotherapy, had been affected by the COVID-19 pandemic.

In the United Kingdom, Cancer Research UK estimated that because of the disruption to cancer services, 2.4 million people did not undergo cancer screening or further testing or did not receive cancer treatment and that tens of thousands of cases have gone undiagnosed.

Similarly, a survey by Macmillan Cancer Support showed that almost half (45%) of cancer patients have experienced delays or cancellations of cancer treatments, or their treatments have been altered as a result of coronavirus, leaving many living in fear. Calling cancer “the forgotten C” of the pandemic, it warned of a potential cancer “time bomb” when, as the number of deaths from COVID-19 falls, cancer returns as the leading cause of death in the United Kingdom.

Last month, a report also predicted that there will be an excess of cancer deaths in both the United States and United Kingdom because of patients not accessing health care services.

The authors calculated that there will be 6270 excess deaths among cancer patients 1 year from now in England and 33,890 excess deaths among cancer patients older than 40 years in the United States.

This article first appeared on Medscape.com.

A model created by the National Cancer Institute predicts that tens of thousands of excess cancer deaths will occur over the next decade as a result of missed screenings, delays in diagnosis, and reductions in oncology care caused by the COVID-19 pandemic.

“As director of NCI, I am deeply concerned about the potential impacts of delayed diagnoses and deferred or modified treatment plans on cancer incidence and mortality,” said Norman “Ned” Sharpless, MD.

“In the past 3 decades, we have seen steady and strong progress against death and suffering from cancer, thanks to improvements in prevention, screening, diagnosis, and treatment. I worry that the SARS-CoV-2 pandemic has put those decades of steady progress at risk and may precipitate reversals of these trends.”

In an editorial published June 19 in Science, Dr. Sharpless highlighted modeling performed by the NCI that predicts an excess of 10,000 deaths from breast and colorectal cancer over the next 10 years.

The number of excess deaths per year would peak in the next year or 2, likely sooner for colorectal than for breast cancer, but “for both cancer types, we believe the pandemic will influence cancer deaths for at least a decade.”

In an interview, Dr. Sharpless pointed out that this analysis is conservative because the researchers only evaluated two types of cancer. They chose breast and colorectal cancer because these are common cancers (accounting for about one-sixth of all cancers) with relatively high screening rates.

“We didn’t model other cancer types, but we have no reason to think that we’re not going to see the same thing with other types of malignancies,” he said. “That is a significant amount of excess mortality.”
 

Delayed diagnosis, modified therapy

One of the effects of the pandemic has been to cause delays in cancer diagnosis. “Routine screening has plummeted and is running at less than 90% in some systems,” Dr. Sharpless said.

“Most cancers are diagnosed when people experience symptoms and go see their doctors, and those symptomatic screening events are also not happening,” he continued. “Fear of contracting the coronavirus in health care settings has dissuaded people from visits.”

In some cases, a delay in diagnosis will allow the cancer to progress to a more advanced stage. “The earlier the diagnosis, the better, and if the stages are more advanced, patients will not do as well for virtually every kind of cancer,” he said.

In addition to delays in diagnosis, treatments are being postponed or modified for patients recently diagnosed with cancer. Because of delays and reductions in curative therapies, patients may be receiving less than optimal care.

“We are seeing a lot of nonstandard care,” said Dr. Sharpless. “All of these things add up to increased cancer morbidity and mortality.”

He also pointed out that the term “elective” is confusing and problematic. “It doesn’t mean that it’s not needed, just that it’s not an emergency and doesn’t need to be done today,” said Dr. Sharpless. “But if we’re talking about chemotherapy and surgery, we don’t think they can be delayed for too long – maybe a week, but not for several months.”

Dr. Sharpless feels that overall it is time for cancer care to resume as much as possible, because “ignoring cancer for too long is an untenable choice and may turn one public health crisis into another.”

“If we act now, we can make up for lost time,” he wrote in the editorial. “Clearly, postponing procedures and deferring care due to the pandemic was prudent at one time, but now that we have made it through the initial shock of the pandemic, I believe it is time to resume robust cancer care.”

Through their network of cancer centers, researchers with the NCI can develop innovative solutions that allow screening and treatment to move forward while maintaining safety. “We need to make patients feel safe, and we have to answer important questions quickly,” he said.
 

Impact of COVID-19 on cancer care

The COVID-19 pandemic has overwhelmed health care systems worldwide and has created major challenges for clinicians who are caring for patients with cancer.

As previously reported, hospitals reprioritized resources for an impending onslaught of COVID-19 patients. Services and procedures deemed to be nonessential were canceled or delayed, including surgeries and imaging.

In a survey conducted by the American Cancer Society Cancer Action Network, half of the 1219 respondents reported changes, delays, or disruptions to the care they were receiving. The services most frequently affected included in-person provider visits (50%), supportive services (20%), and imaging procedures to monitor tumor growth (20%).

In addition, 8% reported that their treatment, including chemotherapy and immunotherapy, had been affected by the COVID-19 pandemic.

In the United Kingdom, Cancer Research UK estimated that because of the disruption to cancer services, 2.4 million people did not undergo cancer screening or further testing or did not receive cancer treatment and that tens of thousands of cases have gone undiagnosed.

Similarly, a survey by Macmillan Cancer Support showed that almost half (45%) of cancer patients have experienced delays or cancellations of cancer treatments, or their treatments have been altered as a result of coronavirus, leaving many living in fear. Calling cancer “the forgotten C” of the pandemic, it warned of a potential cancer “time bomb” when, as the number of deaths from COVID-19 falls, cancer returns as the leading cause of death in the United Kingdom.

Last month, a report also predicted that there will be an excess of cancer deaths in both the United States and United Kingdom because of patients not accessing health care services.

The authors calculated that there will be 6270 excess deaths among cancer patients 1 year from now in England and 33,890 excess deaths among cancer patients older than 40 years in the United States.

This article first appeared on Medscape.com.

A model created by the National Cancer Institute predicts that tens of thousands of excess cancer deaths will occur over the next decade as a result of missed screenings, delays in diagnosis, and reductions in oncology care caused by the COVID-19 pandemic.

“As director of NCI, I am deeply concerned about the potential impacts of delayed diagnoses and deferred or modified treatment plans on cancer incidence and mortality,” said Norman “Ned” Sharpless, MD.

“In the past 3 decades, we have seen steady and strong progress against death and suffering from cancer, thanks to improvements in prevention, screening, diagnosis, and treatment. I worry that the SARS-CoV-2 pandemic has put those decades of steady progress at risk and may precipitate reversals of these trends.”

In an editorial published June 19 in Science, Dr. Sharpless highlighted modeling performed by the NCI that predicts an excess of 10,000 deaths from breast and colorectal cancer over the next 10 years.

The number of excess deaths per year would peak in the next year or 2, likely sooner for colorectal than for breast cancer, but “for both cancer types, we believe the pandemic will influence cancer deaths for at least a decade.”

In an interview, Dr. Sharpless pointed out that this analysis is conservative because the researchers only evaluated two types of cancer. They chose breast and colorectal cancer because these are common cancers (accounting for about one-sixth of all cancers) with relatively high screening rates.

“We didn’t model other cancer types, but we have no reason to think that we’re not going to see the same thing with other types of malignancies,” he said. “That is a significant amount of excess mortality.”
 

Delayed diagnosis, modified therapy

One of the effects of the pandemic has been to cause delays in cancer diagnosis. “Routine screening has plummeted and is running at less than 90% in some systems,” Dr. Sharpless said.

“Most cancers are diagnosed when people experience symptoms and go see their doctors, and those symptomatic screening events are also not happening,” he continued. “Fear of contracting the coronavirus in health care settings has dissuaded people from visits.”

In some cases, a delay in diagnosis will allow the cancer to progress to a more advanced stage. “The earlier the diagnosis, the better, and if the stages are more advanced, patients will not do as well for virtually every kind of cancer,” he said.

In addition to delays in diagnosis, treatments are being postponed or modified for patients recently diagnosed with cancer. Because of delays and reductions in curative therapies, patients may be receiving less than optimal care.

“We are seeing a lot of nonstandard care,” said Dr. Sharpless. “All of these things add up to increased cancer morbidity and mortality.”

He also pointed out that the term “elective” is confusing and problematic. “It doesn’t mean that it’s not needed, just that it’s not an emergency and doesn’t need to be done today,” said Dr. Sharpless. “But if we’re talking about chemotherapy and surgery, we don’t think they can be delayed for too long – maybe a week, but not for several months.”

Dr. Sharpless feels that overall it is time for cancer care to resume as much as possible, because “ignoring cancer for too long is an untenable choice and may turn one public health crisis into another.”

“If we act now, we can make up for lost time,” he wrote in the editorial. “Clearly, postponing procedures and deferring care due to the pandemic was prudent at one time, but now that we have made it through the initial shock of the pandemic, I believe it is time to resume robust cancer care.”

Through their network of cancer centers, researchers with the NCI can develop innovative solutions that allow screening and treatment to move forward while maintaining safety. “We need to make patients feel safe, and we have to answer important questions quickly,” he said.
 

Impact of COVID-19 on cancer care

The COVID-19 pandemic has overwhelmed health care systems worldwide and has created major challenges for clinicians who are caring for patients with cancer.

As previously reported, hospitals reprioritized resources for an impending onslaught of COVID-19 patients. Services and procedures deemed to be nonessential were canceled or delayed, including surgeries and imaging.

In a survey conducted by the American Cancer Society Cancer Action Network, half of the 1219 respondents reported changes, delays, or disruptions to the care they were receiving. The services most frequently affected included in-person provider visits (50%), supportive services (20%), and imaging procedures to monitor tumor growth (20%).

In addition, 8% reported that their treatment, including chemotherapy and immunotherapy, had been affected by the COVID-19 pandemic.

In the United Kingdom, Cancer Research UK estimated that because of the disruption to cancer services, 2.4 million people did not undergo cancer screening or further testing or did not receive cancer treatment and that tens of thousands of cases have gone undiagnosed.

Similarly, a survey by Macmillan Cancer Support showed that almost half (45%) of cancer patients have experienced delays or cancellations of cancer treatments, or their treatments have been altered as a result of coronavirus, leaving many living in fear. Calling cancer “the forgotten C” of the pandemic, it warned of a potential cancer “time bomb” when, as the number of deaths from COVID-19 falls, cancer returns as the leading cause of death in the United Kingdom.

Last month, a report also predicted that there will be an excess of cancer deaths in both the United States and United Kingdom because of patients not accessing health care services.

The authors calculated that there will be 6270 excess deaths among cancer patients 1 year from now in England and 33,890 excess deaths among cancer patients older than 40 years in the United States.

This article first appeared on Medscape.com.

Key findings in metastatic breast cancer, presented at the ASCO 2020 Virtual Annual Meeting, ranged across all tumor subtypes.

Arguably, the top news in breast cancer was a plenary presentation addressing the role of locoregional therapy in advanced disease. Dr. Harold Burstein, of Dana-Farber Cancer Institute, comments that this study indicates systemic therapy as the mainstay treatment for woman with newly diagnosed advanced disease and a tumor in the breast.

In triple-negative breast cancer, Dr. Burstein highlights two studies. The KEYNOTE-355 study validates the addition of a checkpoint inhibitor in first-line therapy in women whose tumors are PD-L1 positive. The intriguing results of the SWOG S1416 trial, Dr. Burstein comments, suggest the use of PARP inhibition may extend beyond BRCA1 and BRCA2 breast cancers.

In HER2-positive breast cancer, an update of the HER2CLIMB study indicates that the combination of tucatinib, trastuzumab, and capecitabine continues to benefit women with HER2-positive disease. Dr. Burstein expects this combination will be a new standard of care, particularly in women with brain metastases.

As for ER-positive breast cancer, Dr. Burstein reviews the BYLieve trial. Results of this study suggest alpelisib has activity in women with a PIK3CA mutation who have already received a CDK4/6 inhibitor.

Harold J. Burstein, Md, PhD

Professor, Department of Medicine, Harvard Medical School; Institute Physician, Dana-Farber Cancer Institute, Boston, Massachusetts. Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships.

Key findings in metastatic breast cancer, presented at the ASCO 2020 Virtual Annual Meeting, ranged across all tumor subtypes.

Arguably, the top news in breast cancer was a plenary presentation addressing the role of locoregional therapy in advanced disease. Dr. Harold Burstein, of Dana-Farber Cancer Institute, comments that this study indicates systemic therapy as the mainstay treatment for woman with newly diagnosed advanced disease and a tumor in the breast.

In triple-negative breast cancer, Dr. Burstein highlights two studies. The KEYNOTE-355 study validates the addition of a checkpoint inhibitor in first-line therapy in women whose tumors are PD-L1 positive. The intriguing results of the SWOG S1416 trial, Dr. Burstein comments, suggest the use of PARP inhibition may extend beyond BRCA1 and BRCA2 breast cancers.

In HER2-positive breast cancer, an update of the HER2CLIMB study indicates that the combination of tucatinib, trastuzumab, and capecitabine continues to benefit women with HER2-positive disease. Dr. Burstein expects this combination will be a new standard of care, particularly in women with brain metastases.

As for ER-positive breast cancer, Dr. Burstein reviews the BYLieve trial. Results of this study suggest alpelisib has activity in women with a PIK3CA mutation who have already received a CDK4/6 inhibitor.

Harold J. Burstein, Md, PhD

Professor, Department of Medicine, Harvard Medical School; Institute Physician, Dana-Farber Cancer Institute, Boston, Massachusetts. Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships.

Key findings in metastatic breast cancer, presented at the ASCO 2020 Virtual Annual Meeting, ranged across all tumor subtypes.

Arguably, the top news in breast cancer was a plenary presentation addressing the role of locoregional therapy in advanced disease. Dr. Harold Burstein, of Dana-Farber Cancer Institute, comments that this study indicates systemic therapy as the mainstay treatment for woman with newly diagnosed advanced disease and a tumor in the breast.

In triple-negative breast cancer, Dr. Burstein highlights two studies. The KEYNOTE-355 study validates the addition of a checkpoint inhibitor in first-line therapy in women whose tumors are PD-L1 positive. The intriguing results of the SWOG S1416 trial, Dr. Burstein comments, suggest the use of PARP inhibition may extend beyond BRCA1 and BRCA2 breast cancers.

In HER2-positive breast cancer, an update of the HER2CLIMB study indicates that the combination of tucatinib, trastuzumab, and capecitabine continues to benefit women with HER2-positive disease. Dr. Burstein expects this combination will be a new standard of care, particularly in women with brain metastases.

As for ER-positive breast cancer, Dr. Burstein reviews the BYLieve trial. Results of this study suggest alpelisib has activity in women with a PIK3CA mutation who have already received a CDK4/6 inhibitor.

Harold J. Burstein, Md, PhD

Professor, Department of Medicine, Harvard Medical School; Institute Physician, Dana-Farber Cancer Institute, Boston, Massachusetts. Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships.

Specialty care from a cardiologist may confer clinical benefits for women with HER2-positive breast cancer treated with trastuzumab, a new study suggests.

Over 48 months of follow-up, results showed cardiology involvement prior to starting trastuzumab was associated with a higher rate of guideline-recommended cardiovascular (CV) monitoring and better systolic blood pressure (BP) control.

Trastuzumab is commonly used to treat HER2-positive breast cancer, which accounts for 20% of all breast cancers. But it carries a boxed warning for decreased left ventricular ejection fraction and heart failure (HF), and interval monitoring with echocardiography is recommended for all patients receiving the monoclonal antibody.

For the study, investigators analyzed electronic health records from 1,047 patients (mean age, 54 years) who received trastuzumab between January 2009 and July 2018 in the University of Pennsylvania health system, Philadelphia. Anthracyclines were used as part of treatment in 15% of patients.

Guideline-adherent cardiovascular monitoring was defined as echocardiography assessment in the 4 months before the initiation of trastuzumab and at least every 4 months during therapy.

Overall, 28% of patients visited a cardiology or cardio-oncology provider beginning 3 months before the baseline visit until the last contact date, the authors reported in JACC: CardioOncology.

Pre-existing HF, atrial fibrillation, and anthracycline treatment were independently associated with a cardiology visit either at baseline or during follow-up.

Patients who interacted with cardiologists, compared with those who did not, had more guideline-adherent cardiac monitoring (76.4% vs 60.1%; P = .007) and cardiac biomarker testing with troponin or N-terminal pro-B-type natriuretic peptide (27.8% vs 13.8%; P = .001).

The use of guideline-adherent cardiac monitoring was 36% to 46% in previous studies of patients with breast cancer treated with adjuvant trastuzumab-based therapy, the authors note.

Among the 5,815 echocardiographic procedures for which data on provider specialty were documented, most of the orders were authorized by oncologists (approximately 84% in those with no cardiology involvement and approximately 79% in those with cardiology involvement before trastuzumab initiation).
 

CV risk parameters

Cardiology involvement was associated with an average 1.5 mm Hg lower systolic BP, independent of baseline systolic BP and antihypertensive medication use (95% confidence interval, –2.9 to –0.1; P = .035).

The effect size was greater in patients with baseline hypertension, who had an average 2.7 mm Hg drop in systolic BP (95% CI, –4.6 to –0.7; P = .007) and were more likely to attain a target systolic BP below 140 mm Hg (odds ratio, 1.36; 95% CI, 1.06 to 1.74; P = .016).

Body mass index (BMI) did not budge significantly in the overall population when cardiologists were involved, but it dropped 0.5 kg/m2 in women who were overweight or obese at baseline.

“I think the results are encouraging,” senior author Bonnie Ky, MD, MSCE, University of Pennsylvania, told theheart.org | Medscape Cardiology. “These are modest changes but they are significant.”

These types of changes have been associated with significant reductions in cardiovascular disease risk over time in larger clinical trials, she noted. For example, a 2 mm Hg reduction in systolic BP has been linked to a 10% reduction in stroke mortality and a 7% reduction in ischemic heart disease mortality in middle-aged adults.

“We do think they are important and speak to more aggressive risk factor modification under the care of a specialist,” said Ky, who is also editor-in-chief of JACC: CardioOncology.

This broader role for cardiologists is particularly important given the burden of pre-existing CVD and CVD risk factors in patients with cancer and survivors. In the study, the baseline prevalence of hypertension was 40.6%, dyslipidemia 23.1%, HF 3.2%, atrial fibrillation 1.7%, and diabetes 5.9%.

“Ideally, collaboration between cardiology and oncology can improve the ability to cure a patient’s cancer while minimizing the risk of adverse cardiovascular occurrences,” Erica L. Mayer, MD, MPH, Dana-Farber Cancer Institute, Boston, told theheart.org | Medscape Cardiology. “Optimization of all cardiovascular parameters, including blood pressure, lipids, and weight, may allow a patient to protect her heart health while becoming a healthy cancer survivor.”

When asked about the 28% cardiology involvement at a U.S. cancer center with one of the most well-developed cardio-oncology programs, she said “the linkage with pre-existing cardiovascular conditions, as well as the likelihood of low incidence of cardiovascular disease, in the study population may have led to what appears to be a lower percentage of patients interacting with cardiology at baseline.”

In an accompanying editorial, Mayer says a case can be made from the findings that patients with pre-existing CV disease or at high risk for adverse CV events with cancer therapy should receive multidisciplinary care that involves a cardiologist. “However, for young, otherwise healthy patients with breast cancer with few or no cardiovascular risk factors, the benefits of [additional] subspecialty care may be less clear.”

Further, the rationale supporting the recommended frequency of cardiac monitoring may not be as “compelling” in this group, given the very low incidence of baseline cardiac dysfunction or cardiac events, particularly when treated with nonanthracycline regimens, she writes.

The findings are a call for further study and more personalized medicine, agreed Ky.

“I think there’s a need absolutely for established guidelines and/or expert consensus statements about who should be referred so patients can be referred more systematically,” she said. “Referral to cardiologists, however, is certainly a function of risk factors. Part of the challenge is identifying who will derive the most benefit from cardiovascular care.

“There are some obvious cases: Patients with heart failure and patients with pre-existing cardiovascular disease should be under the regular care of a cardiologist,” Ky added. “But there’s certainly a gray zone, especially as it relates, for example, to patients with hypertension and cardiovascular risk factors. It’s not a ‘one size fits all,’ and I believe it is a matter of defining who is at increased CV risk and who would derive the greatest clinical benefit.”

Researchers at the University of Pennsylvania have developed a clinical risk–prediction algorithm and are investigating both clinical- and biomarker-guided strategies to identify and treat patients at greatest risk of developing left ventricular declines and cardiac dysfunction with exposure to cancer therapies. “These studies are one step forward, but they will all need to be externally validated,” Ky said.

Ky and Mayer reported having no relevant conflicts of interest.

This article first appeared on Medscape.com.

Specialty care from a cardiologist may confer clinical benefits for women with HER2-positive breast cancer treated with trastuzumab, a new study suggests.

Over 48 months of follow-up, results showed cardiology involvement prior to starting trastuzumab was associated with a higher rate of guideline-recommended cardiovascular (CV) monitoring and better systolic blood pressure (BP) control.

Trastuzumab is commonly used to treat HER2-positive breast cancer, which accounts for 20% of all breast cancers. But it carries a boxed warning for decreased left ventricular ejection fraction and heart failure (HF), and interval monitoring with echocardiography is recommended for all patients receiving the monoclonal antibody.

For the study, investigators analyzed electronic health records from 1,047 patients (mean age, 54 years) who received trastuzumab between January 2009 and July 2018 in the University of Pennsylvania health system, Philadelphia. Anthracyclines were used as part of treatment in 15% of patients.

Guideline-adherent cardiovascular monitoring was defined as echocardiography assessment in the 4 months before the initiation of trastuzumab and at least every 4 months during therapy.

Overall, 28% of patients visited a cardiology or cardio-oncology provider beginning 3 months before the baseline visit until the last contact date, the authors reported in JACC: CardioOncology.

Pre-existing HF, atrial fibrillation, and anthracycline treatment were independently associated with a cardiology visit either at baseline or during follow-up.

Patients who interacted with cardiologists, compared with those who did not, had more guideline-adherent cardiac monitoring (76.4% vs 60.1%; P = .007) and cardiac biomarker testing with troponin or N-terminal pro-B-type natriuretic peptide (27.8% vs 13.8%; P = .001).

The use of guideline-adherent cardiac monitoring was 36% to 46% in previous studies of patients with breast cancer treated with adjuvant trastuzumab-based therapy, the authors note.

Among the 5,815 echocardiographic procedures for which data on provider specialty were documented, most of the orders were authorized by oncologists (approximately 84% in those with no cardiology involvement and approximately 79% in those with cardiology involvement before trastuzumab initiation).
 

CV risk parameters

Cardiology involvement was associated with an average 1.5 mm Hg lower systolic BP, independent of baseline systolic BP and antihypertensive medication use (95% confidence interval, –2.9 to –0.1; P = .035).

The effect size was greater in patients with baseline hypertension, who had an average 2.7 mm Hg drop in systolic BP (95% CI, –4.6 to –0.7; P = .007) and were more likely to attain a target systolic BP below 140 mm Hg (odds ratio, 1.36; 95% CI, 1.06 to 1.74; P = .016).

Body mass index (BMI) did not budge significantly in the overall population when cardiologists were involved, but it dropped 0.5 kg/m2 in women who were overweight or obese at baseline.

“I think the results are encouraging,” senior author Bonnie Ky, MD, MSCE, University of Pennsylvania, told theheart.org | Medscape Cardiology. “These are modest changes but they are significant.”

These types of changes have been associated with significant reductions in cardiovascular disease risk over time in larger clinical trials, she noted. For example, a 2 mm Hg reduction in systolic BP has been linked to a 10% reduction in stroke mortality and a 7% reduction in ischemic heart disease mortality in middle-aged adults.

“We do think they are important and speak to more aggressive risk factor modification under the care of a specialist,” said Ky, who is also editor-in-chief of JACC: CardioOncology.

This broader role for cardiologists is particularly important given the burden of pre-existing CVD and CVD risk factors in patients with cancer and survivors. In the study, the baseline prevalence of hypertension was 40.6%, dyslipidemia 23.1%, HF 3.2%, atrial fibrillation 1.7%, and diabetes 5.9%.

“Ideally, collaboration between cardiology and oncology can improve the ability to cure a patient’s cancer while minimizing the risk of adverse cardiovascular occurrences,” Erica L. Mayer, MD, MPH, Dana-Farber Cancer Institute, Boston, told theheart.org | Medscape Cardiology. “Optimization of all cardiovascular parameters, including blood pressure, lipids, and weight, may allow a patient to protect her heart health while becoming a healthy cancer survivor.”

When asked about the 28% cardiology involvement at a U.S. cancer center with one of the most well-developed cardio-oncology programs, she said “the linkage with pre-existing cardiovascular conditions, as well as the likelihood of low incidence of cardiovascular disease, in the study population may have led to what appears to be a lower percentage of patients interacting with cardiology at baseline.”

In an accompanying editorial, Mayer says a case can be made from the findings that patients with pre-existing CV disease or at high risk for adverse CV events with cancer therapy should receive multidisciplinary care that involves a cardiologist. “However, for young, otherwise healthy patients with breast cancer with few or no cardiovascular risk factors, the benefits of [additional] subspecialty care may be less clear.”

Further, the rationale supporting the recommended frequency of cardiac monitoring may not be as “compelling” in this group, given the very low incidence of baseline cardiac dysfunction or cardiac events, particularly when treated with nonanthracycline regimens, she writes.

The findings are a call for further study and more personalized medicine, agreed Ky.

“I think there’s a need absolutely for established guidelines and/or expert consensus statements about who should be referred so patients can be referred more systematically,” she said. “Referral to cardiologists, however, is certainly a function of risk factors. Part of the challenge is identifying who will derive the most benefit from cardiovascular care.

“There are some obvious cases: Patients with heart failure and patients with pre-existing cardiovascular disease should be under the regular care of a cardiologist,” Ky added. “But there’s certainly a gray zone, especially as it relates, for example, to patients with hypertension and cardiovascular risk factors. It’s not a ‘one size fits all,’ and I believe it is a matter of defining who is at increased CV risk and who would derive the greatest clinical benefit.”

Researchers at the University of Pennsylvania have developed a clinical risk–prediction algorithm and are investigating both clinical- and biomarker-guided strategies to identify and treat patients at greatest risk of developing left ventricular declines and cardiac dysfunction with exposure to cancer therapies. “These studies are one step forward, but they will all need to be externally validated,” Ky said.

Ky and Mayer reported having no relevant conflicts of interest.

This article first appeared on Medscape.com.

Specialty care from a cardiologist may confer clinical benefits for women with HER2-positive breast cancer treated with trastuzumab, a new study suggests.

Over 48 months of follow-up, results showed cardiology involvement prior to starting trastuzumab was associated with a higher rate of guideline-recommended cardiovascular (CV) monitoring and better systolic blood pressure (BP) control.

Trastuzumab is commonly used to treat HER2-positive breast cancer, which accounts for 20% of all breast cancers. But it carries a boxed warning for decreased left ventricular ejection fraction and heart failure (HF), and interval monitoring with echocardiography is recommended for all patients receiving the monoclonal antibody.

For the study, investigators analyzed electronic health records from 1,047 patients (mean age, 54 years) who received trastuzumab between January 2009 and July 2018 in the University of Pennsylvania health system, Philadelphia. Anthracyclines were used as part of treatment in 15% of patients.

Guideline-adherent cardiovascular monitoring was defined as echocardiography assessment in the 4 months before the initiation of trastuzumab and at least every 4 months during therapy.

Overall, 28% of patients visited a cardiology or cardio-oncology provider beginning 3 months before the baseline visit until the last contact date, the authors reported in JACC: CardioOncology.

Pre-existing HF, atrial fibrillation, and anthracycline treatment were independently associated with a cardiology visit either at baseline or during follow-up.

Patients who interacted with cardiologists, compared with those who did not, had more guideline-adherent cardiac monitoring (76.4% vs 60.1%; P = .007) and cardiac biomarker testing with troponin or N-terminal pro-B-type natriuretic peptide (27.8% vs 13.8%; P = .001).

The use of guideline-adherent cardiac monitoring was 36% to 46% in previous studies of patients with breast cancer treated with adjuvant trastuzumab-based therapy, the authors note.

Among the 5,815 echocardiographic procedures for which data on provider specialty were documented, most of the orders were authorized by oncologists (approximately 84% in those with no cardiology involvement and approximately 79% in those with cardiology involvement before trastuzumab initiation).
 

CV risk parameters

Cardiology involvement was associated with an average 1.5 mm Hg lower systolic BP, independent of baseline systolic BP and antihypertensive medication use (95% confidence interval, –2.9 to –0.1; P = .035).

The effect size was greater in patients with baseline hypertension, who had an average 2.7 mm Hg drop in systolic BP (95% CI, –4.6 to –0.7; P = .007) and were more likely to attain a target systolic BP below 140 mm Hg (odds ratio, 1.36; 95% CI, 1.06 to 1.74; P = .016).

Body mass index (BMI) did not budge significantly in the overall population when cardiologists were involved, but it dropped 0.5 kg/m2 in women who were overweight or obese at baseline.

“I think the results are encouraging,” senior author Bonnie Ky, MD, MSCE, University of Pennsylvania, told theheart.org | Medscape Cardiology. “These are modest changes but they are significant.”

These types of changes have been associated with significant reductions in cardiovascular disease risk over time in larger clinical trials, she noted. For example, a 2 mm Hg reduction in systolic BP has been linked to a 10% reduction in stroke mortality and a 7% reduction in ischemic heart disease mortality in middle-aged adults.

“We do think they are important and speak to more aggressive risk factor modification under the care of a specialist,” said Ky, who is also editor-in-chief of JACC: CardioOncology.

This broader role for cardiologists is particularly important given the burden of pre-existing CVD and CVD risk factors in patients with cancer and survivors. In the study, the baseline prevalence of hypertension was 40.6%, dyslipidemia 23.1%, HF 3.2%, atrial fibrillation 1.7%, and diabetes 5.9%.

“Ideally, collaboration between cardiology and oncology can improve the ability to cure a patient’s cancer while minimizing the risk of adverse cardiovascular occurrences,” Erica L. Mayer, MD, MPH, Dana-Farber Cancer Institute, Boston, told theheart.org | Medscape Cardiology. “Optimization of all cardiovascular parameters, including blood pressure, lipids, and weight, may allow a patient to protect her heart health while becoming a healthy cancer survivor.”

When asked about the 28% cardiology involvement at a U.S. cancer center with one of the most well-developed cardio-oncology programs, she said “the linkage with pre-existing cardiovascular conditions, as well as the likelihood of low incidence of cardiovascular disease, in the study population may have led to what appears to be a lower percentage of patients interacting with cardiology at baseline.”

In an accompanying editorial, Mayer says a case can be made from the findings that patients with pre-existing CV disease or at high risk for adverse CV events with cancer therapy should receive multidisciplinary care that involves a cardiologist. “However, for young, otherwise healthy patients with breast cancer with few or no cardiovascular risk factors, the benefits of [additional] subspecialty care may be less clear.”

Further, the rationale supporting the recommended frequency of cardiac monitoring may not be as “compelling” in this group, given the very low incidence of baseline cardiac dysfunction or cardiac events, particularly when treated with nonanthracycline regimens, she writes.

The findings are a call for further study and more personalized medicine, agreed Ky.

“I think there’s a need absolutely for established guidelines and/or expert consensus statements about who should be referred so patients can be referred more systematically,” she said. “Referral to cardiologists, however, is certainly a function of risk factors. Part of the challenge is identifying who will derive the most benefit from cardiovascular care.

“There are some obvious cases: Patients with heart failure and patients with pre-existing cardiovascular disease should be under the regular care of a cardiologist,” Ky added. “But there’s certainly a gray zone, especially as it relates, for example, to patients with hypertension and cardiovascular risk factors. It’s not a ‘one size fits all,’ and I believe it is a matter of defining who is at increased CV risk and who would derive the greatest clinical benefit.”

Researchers at the University of Pennsylvania have developed a clinical risk–prediction algorithm and are investigating both clinical- and biomarker-guided strategies to identify and treat patients at greatest risk of developing left ventricular declines and cardiac dysfunction with exposure to cancer therapies. “These studies are one step forward, but they will all need to be externally validated,” Ky said.

Ky and Mayer reported having no relevant conflicts of interest.

This article first appeared on Medscape.com.

In its updated cancer prevention guidelines, the American Cancer Society now recommends that “it is best not to drink alcohol.”

Previously, ACS suggested that, for those who consume alcoholic beverages, intake should be no more than one drink per day for women or two per day for men. That recommendation is still in place, but is now accompanied by this new, stronger directive.

The revised guidelines also place more emphasis on reducing the consumption of processed and red meat and highly processed foods, and on increasing physical activity.

But importantly, there is also a call for action from public, private, and community organizations to work to together to increase access to affordable, nutritious foods and physical activity.

“Making healthy choices can be challenging for many, and there are strategies included in the guidelines that communities can undertake to help reduce barriers to eating well and physical activity,” said Laura Makaroff, DO, American Cancer Society senior vice president. “Individual choice is an important part of a healthy lifestyle, but having the right policies and environmental factors to break down these barriers is also important, and that is something that clinicians can support.”

The guidelines were published in CA: A Cancer Journal for Clinicians.

The link between cancer and lifestyle factors has long been established, and for the past 4 decades, both government and leading nonprofit health organizations, including the ACS and the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR), have released cancer prevention guidelines and recommendations that focus on managing weight, diet, physical activity, and alcohol consumption.

In 2012, the ACS issued guidelines on diet and physical activity, and their current guideline is largely based on the WCRF/AICR systematic reviews and Continuous Update Project reports, which were last updated in 2018. The ACS guidelines also incorporated systematic reviews conducted by the International Agency on Cancer Research (IARC) and the U.S. Department of Agriculture and the Department of Health and Human Services (USDA/HHS) and other analyses that were published since the WCRF/AICR recommendations were released.
 

Emphasis on three areas

The differences between the old guidelines and the update do not differ dramatically, but Makaroff highlighted a few areas that have increased emphasis.

Time spent being physically active is critical. The recommendation has changed to encourage adults to engage in 150-300 minutes (2.5-5 hours) of moderate-intensity physical activity, or 75-150 minutes (1.25-2.5 hours) of vigorous-intensity physical activity, or an equivalent combination, per week. Achieving or exceeding the upper limit of 300 minutes is optimal.

“That is more than what we have recommended in the past, along with the continued message that children and adolescents engage in at least 1 hour of moderate- or vigorous-intensity activity each day,” she told Medscape Medical News.

The ACS has also increased emphasis on reducing the consumption of processed and red meat. “This is part of a healthy eating pattern and making sure that people are eating food that is high in nutrients that help achieve and maintain a healthy body weight,” said Makaroff.

A healthy diet should include a variety of dark green, red, and orange vegetables; fiber-rich legumes; and fruits with a variety of colors and whole grains, according to the guidelines. Sugar-sweetened beverages, highly processed foods, and refined grain products should be limited or avoided.

The revised dietary recommendations reflect a shift from a “reductionist or nutrient-centric” approach to one that is more “holistic” and that focuses on dietary patterns. In contrast to a focus on individual nutrients and bioactive compounds, the new approach is more consistent with what and how people actually eat, ACS points out.

The third area that Makaroff highlighted is alcohol, where the recommendation is to avoid or limit consumption. “The current update says not to drink alcohol, which is in line with the scientific evidence, but for those people who choose to drink alcohol, to limit it to one drink per day for women and two drinks per day for men.”

Thus, the change here is that the previous guideline only recommended limiting alcohol consumption, while the update suggests that, optimally, it should be avoided completely.

The ACS has also called for community involvement to help implement these goals: “Public, private, and community organizations should work collaboratively at national, state, and local levels to develop, advocate for, and implement policy and environmental changes that increase access to affordable, nutritious foods; provide safe, enjoyable, and accessible opportunities for physical activity; and limit alcohol for all individuals.”
 

No smoking guns

Commenting on the guidelines, Steven K. Clinton, MD, PhD, associate director of the Center for Advanced Functional Foods Research and Entrepreneurship at the Ohio State University, Columbus, explained that he didn’t view the change in alcohol as that much of an evolution. “It’s been 8 years since they revised their overall guidelines, and during that time frame, there has been an enormous growth in the evidence that has been used by many organizations,” he said.

Clinton noted that the guidelines are consistent with the whole body of current scientific literature. “It’s very easy to go to the document and look for the ‘smoking gun’ – but the smoking gun is really not one thing,” he said. “It’s a pattern, and what dietitians and nutritionists are telling people is that you need to orchestrate a healthy lifestyle and diet, with a diet that has a foundation of fruits, vegetables, whole grains, and modest intake of refined grains and meat. You are orchestrating an entire pattern to get the maximum benefit.”

Makaroff is an employee of the ACS. Clinton has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In its updated cancer prevention guidelines, the American Cancer Society now recommends that “it is best not to drink alcohol.”

Previously, ACS suggested that, for those who consume alcoholic beverages, intake should be no more than one drink per day for women or two per day for men. That recommendation is still in place, but is now accompanied by this new, stronger directive.

The revised guidelines also place more emphasis on reducing the consumption of processed and red meat and highly processed foods, and on increasing physical activity.

But importantly, there is also a call for action from public, private, and community organizations to work to together to increase access to affordable, nutritious foods and physical activity.

“Making healthy choices can be challenging for many, and there are strategies included in the guidelines that communities can undertake to help reduce barriers to eating well and physical activity,” said Laura Makaroff, DO, American Cancer Society senior vice president. “Individual choice is an important part of a healthy lifestyle, but having the right policies and environmental factors to break down these barriers is also important, and that is something that clinicians can support.”

The guidelines were published in CA: A Cancer Journal for Clinicians.

The link between cancer and lifestyle factors has long been established, and for the past 4 decades, both government and leading nonprofit health organizations, including the ACS and the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR), have released cancer prevention guidelines and recommendations that focus on managing weight, diet, physical activity, and alcohol consumption.

In 2012, the ACS issued guidelines on diet and physical activity, and their current guideline is largely based on the WCRF/AICR systematic reviews and Continuous Update Project reports, which were last updated in 2018. The ACS guidelines also incorporated systematic reviews conducted by the International Agency on Cancer Research (IARC) and the U.S. Department of Agriculture and the Department of Health and Human Services (USDA/HHS) and other analyses that were published since the WCRF/AICR recommendations were released.
 

Emphasis on three areas

The differences between the old guidelines and the update do not differ dramatically, but Makaroff highlighted a few areas that have increased emphasis.

Time spent being physically active is critical. The recommendation has changed to encourage adults to engage in 150-300 minutes (2.5-5 hours) of moderate-intensity physical activity, or 75-150 minutes (1.25-2.5 hours) of vigorous-intensity physical activity, or an equivalent combination, per week. Achieving or exceeding the upper limit of 300 minutes is optimal.

“That is more than what we have recommended in the past, along with the continued message that children and adolescents engage in at least 1 hour of moderate- or vigorous-intensity activity each day,” she told Medscape Medical News.

The ACS has also increased emphasis on reducing the consumption of processed and red meat. “This is part of a healthy eating pattern and making sure that people are eating food that is high in nutrients that help achieve and maintain a healthy body weight,” said Makaroff.

A healthy diet should include a variety of dark green, red, and orange vegetables; fiber-rich legumes; and fruits with a variety of colors and whole grains, according to the guidelines. Sugar-sweetened beverages, highly processed foods, and refined grain products should be limited or avoided.

The revised dietary recommendations reflect a shift from a “reductionist or nutrient-centric” approach to one that is more “holistic” and that focuses on dietary patterns. In contrast to a focus on individual nutrients and bioactive compounds, the new approach is more consistent with what and how people actually eat, ACS points out.

The third area that Makaroff highlighted is alcohol, where the recommendation is to avoid or limit consumption. “The current update says not to drink alcohol, which is in line with the scientific evidence, but for those people who choose to drink alcohol, to limit it to one drink per day for women and two drinks per day for men.”

Thus, the change here is that the previous guideline only recommended limiting alcohol consumption, while the update suggests that, optimally, it should be avoided completely.

The ACS has also called for community involvement to help implement these goals: “Public, private, and community organizations should work collaboratively at national, state, and local levels to develop, advocate for, and implement policy and environmental changes that increase access to affordable, nutritious foods; provide safe, enjoyable, and accessible opportunities for physical activity; and limit alcohol for all individuals.”
 

No smoking guns

Commenting on the guidelines, Steven K. Clinton, MD, PhD, associate director of the Center for Advanced Functional Foods Research and Entrepreneurship at the Ohio State University, Columbus, explained that he didn’t view the change in alcohol as that much of an evolution. “It’s been 8 years since they revised their overall guidelines, and during that time frame, there has been an enormous growth in the evidence that has been used by many organizations,” he said.

Clinton noted that the guidelines are consistent with the whole body of current scientific literature. “It’s very easy to go to the document and look for the ‘smoking gun’ – but the smoking gun is really not one thing,” he said. “It’s a pattern, and what dietitians and nutritionists are telling people is that you need to orchestrate a healthy lifestyle and diet, with a diet that has a foundation of fruits, vegetables, whole grains, and modest intake of refined grains and meat. You are orchestrating an entire pattern to get the maximum benefit.”

Makaroff is an employee of the ACS. Clinton has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In its updated cancer prevention guidelines, the American Cancer Society now recommends that “it is best not to drink alcohol.”

Previously, ACS suggested that, for those who consume alcoholic beverages, intake should be no more than one drink per day for women or two per day for men. That recommendation is still in place, but is now accompanied by this new, stronger directive.

The revised guidelines also place more emphasis on reducing the consumption of processed and red meat and highly processed foods, and on increasing physical activity.

But importantly, there is also a call for action from public, private, and community organizations to work to together to increase access to affordable, nutritious foods and physical activity.

“Making healthy choices can be challenging for many, and there are strategies included in the guidelines that communities can undertake to help reduce barriers to eating well and physical activity,” said Laura Makaroff, DO, American Cancer Society senior vice president. “Individual choice is an important part of a healthy lifestyle, but having the right policies and environmental factors to break down these barriers is also important, and that is something that clinicians can support.”

The guidelines were published in CA: A Cancer Journal for Clinicians.

The link between cancer and lifestyle factors has long been established, and for the past 4 decades, both government and leading nonprofit health organizations, including the ACS and the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR), have released cancer prevention guidelines and recommendations that focus on managing weight, diet, physical activity, and alcohol consumption.

In 2012, the ACS issued guidelines on diet and physical activity, and their current guideline is largely based on the WCRF/AICR systematic reviews and Continuous Update Project reports, which were last updated in 2018. The ACS guidelines also incorporated systematic reviews conducted by the International Agency on Cancer Research (IARC) and the U.S. Department of Agriculture and the Department of Health and Human Services (USDA/HHS) and other analyses that were published since the WCRF/AICR recommendations were released.
 

Emphasis on three areas

The differences between the old guidelines and the update do not differ dramatically, but Makaroff highlighted a few areas that have increased emphasis.

Time spent being physically active is critical. The recommendation has changed to encourage adults to engage in 150-300 minutes (2.5-5 hours) of moderate-intensity physical activity, or 75-150 minutes (1.25-2.5 hours) of vigorous-intensity physical activity, or an equivalent combination, per week. Achieving or exceeding the upper limit of 300 minutes is optimal.

“That is more than what we have recommended in the past, along with the continued message that children and adolescents engage in at least 1 hour of moderate- or vigorous-intensity activity each day,” she told Medscape Medical News.

The ACS has also increased emphasis on reducing the consumption of processed and red meat. “This is part of a healthy eating pattern and making sure that people are eating food that is high in nutrients that help achieve and maintain a healthy body weight,” said Makaroff.

A healthy diet should include a variety of dark green, red, and orange vegetables; fiber-rich legumes; and fruits with a variety of colors and whole grains, according to the guidelines. Sugar-sweetened beverages, highly processed foods, and refined grain products should be limited or avoided.

The revised dietary recommendations reflect a shift from a “reductionist or nutrient-centric” approach to one that is more “holistic” and that focuses on dietary patterns. In contrast to a focus on individual nutrients and bioactive compounds, the new approach is more consistent with what and how people actually eat, ACS points out.

The third area that Makaroff highlighted is alcohol, where the recommendation is to avoid or limit consumption. “The current update says not to drink alcohol, which is in line with the scientific evidence, but for those people who choose to drink alcohol, to limit it to one drink per day for women and two drinks per day for men.”

Thus, the change here is that the previous guideline only recommended limiting alcohol consumption, while the update suggests that, optimally, it should be avoided completely.

The ACS has also called for community involvement to help implement these goals: “Public, private, and community organizations should work collaboratively at national, state, and local levels to develop, advocate for, and implement policy and environmental changes that increase access to affordable, nutritious foods; provide safe, enjoyable, and accessible opportunities for physical activity; and limit alcohol for all individuals.”
 

No smoking guns

Commenting on the guidelines, Steven K. Clinton, MD, PhD, associate director of the Center for Advanced Functional Foods Research and Entrepreneurship at the Ohio State University, Columbus, explained that he didn’t view the change in alcohol as that much of an evolution. “It’s been 8 years since they revised their overall guidelines, and during that time frame, there has been an enormous growth in the evidence that has been used by many organizations,” he said.

Clinton noted that the guidelines are consistent with the whole body of current scientific literature. “It’s very easy to go to the document and look for the ‘smoking gun’ – but the smoking gun is really not one thing,” he said. “It’s a pattern, and what dietitians and nutritionists are telling people is that you need to orchestrate a healthy lifestyle and diet, with a diet that has a foundation of fruits, vegetables, whole grains, and modest intake of refined grains and meat. You are orchestrating an entire pattern to get the maximum benefit.”

Makaroff is an employee of the ACS. Clinton has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic.

In early April, as the COVID-19 surge was bearing down on New York City, those treatment decisions were “a juggling act every single day,” Jonathan Yang, MD, PhD, a radiation oncologist from New York’s Memorial Sloan Kettering Cancer Center, told Medscape Medical News.

Eventually, a glut of guidelines, recommendations, and expert opinions aimed at helping oncologists emerged. The tools help navigate the complicated risk-benefit analysis of their patient’s risk of infection by SARS-CoV-2 and delaying therapy.

Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help?
 

Three-Tier Systems Are Not Very Sophisticated

OncCOVID, a free tool that was launched May 26 by the University of Michigan, allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care.

Combining these personal details with data from the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registry and the National Cancer Database, the Michigan app then estimates a patient’s 5- or 10-year survival with immediate vs delayed treatment and weighs that against their risk for COVID-19 using data from the Johns Hopkins Coronavirus Resource Center.

“We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine.

Spratt explained that almost every organization, professional society, and government has created something like a three-tier system. Tier 1 represents urgent cases and patients who need immediate treatment. For tier 2, treatment can be delayed weeks or a month, and with tier 3, it can be delayed until the pandemic is over or it’s deemed safe.

“[This system] sounds good at first glance, but in cancer, we’re always talking about personalized medicine, and it’s mind-blowing that these tier systems are only based on urgency and prognosis,” he told Medscape Medical News.

Spratt offered an example. Consider a patient with a very aggressive brain tumor ― that patient is in tier 1 and should undergo treatment immediately. But will the treatment actually help? And how helpful would the procedure be if, say, the patient is 80 years old and, if infected, would have a 30% to 50% chance of dying from the coronavirus?

“If the model says this guy has a 5% harm and this one has 30% harm, you can use that to help prioritize,” summarized Spratt.

The app can generate risk estimates for patients living anywhere in the world and has already been accessed by people from 37 countries. However, Spratt cautions that it is primarily “designed and calibrated for the US.

“The estimates are based on very large US registries, and though it’s probably somewhat similar across much of the world, there’s probably certain cancer types that are more region specific ― especially something like stomach cancer or certain types of head and neck cancer in parts of Asia, for example,” he said.

Although the app’s COVID-19 data are specific to the county level in the United States, elsewhere in the world, it is only country specific.

“We’re using the best data we have for coronavirus, but everyone knows we still have large data gaps,” he acknowledged.
 

How Accurate?

Asked to comment on the app, Richard Bleicher, MD, leader of the Breast Cancer Program at Fox Chase Cancer Center, Philadelphia, praised the effort and the goal but had some concerns.

“Several questions arise, most important of which is, How accurate is this, and how has this been validated, if at all ― especially as it is too soon to see the outcomes of patients affected in this pandemic?” he told Medscape Medical News.

“We are imposing delays on a broad scale because of the coronavirus, and we are getting continuously changing data as we test more patients. But both situations are novel and may not be accurately represented by the data being pulled, because the datasets use patients from a few years ago, and confounders in these datasets may not apply to this situation,” Bleicher continued.

Although acknowledging the “value in delineating the risk of dying from cancer vs the risk of dying from the SARS-CoV-2 pandemic,” Bleicher urged caution in using the tool to make individual patient decisions.

“We need to remember that the best of modeling ... can be wildly inaccurate and needs to be validated using patients having the circumstances in question. ... This won’t be possible until long after the pandemic is completed, and so the model’s accuracy remains unknown.”

That sentiment was echoed by Giampaolo Bianchini, MD, head of the Breast Cancer Group, Department of Medical Oncology, Ospedale San Raffaele, in Milan, Italy.

“Arbitrarily postponing and modifying treatment strategies including surgery, radiation therapy, and medical therapy without properly balancing the risk/benefit ratio may lead to significantly worse cancer-related outcomes, which largely exceed the actual risks for COVID,” he wrote in an email.

“The OncCOVID app is a remarkable attempt to fill the gap between perception and estimation,” he said. The app provides side by side the COVID-19 risk estimation and the consequences of arbitrary deviation from the standard of care, observed Bianchini.

However, he pointed out weaknesses, including the fact that the “data generated in literature are not always of high quality and do not take into consideration relevant characteristics of the disease and treatment benefit. It should for sure be used, but then also interpreted with caution.”

Another Italian group responded more positively.

“In our opinion, it could be a useful tool for clinicians,” wrote colleagues Alessio Cortelinni and Giampiero Porzio, both medical oncologists at San Salvatore Hospital and the University of L’Aquila, in Italy. “This Web app might assist clinicians in balancing the risk/benefit ratio of being treated and/or access to the outpatient cancer center for each kind of patient (both early and advanced stages), in order to make a more tailored counseling,” they wrote in an email. “Importantly, the Web app might help those clinicians who work ‘alone,’ in peripheral centers, without resources, colleagues, and multidisciplinary tumor boards on whom they can rely.”

Bleicher, who was involved in the COVID-19 Breast Cancer Consortium’s recommendations for prioritizing breast cancer treatment, summarized that the app “may end up being close or accurate, but we won’t know except in hindsight.”
 

This article first appeared on Medscape.com.

Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic.

In early April, as the COVID-19 surge was bearing down on New York City, those treatment decisions were “a juggling act every single day,” Jonathan Yang, MD, PhD, a radiation oncologist from New York’s Memorial Sloan Kettering Cancer Center, told Medscape Medical News.

Eventually, a glut of guidelines, recommendations, and expert opinions aimed at helping oncologists emerged. The tools help navigate the complicated risk-benefit analysis of their patient’s risk of infection by SARS-CoV-2 and delaying therapy.

Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help?
 

Three-Tier Systems Are Not Very Sophisticated

OncCOVID, a free tool that was launched May 26 by the University of Michigan, allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care.

Combining these personal details with data from the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registry and the National Cancer Database, the Michigan app then estimates a patient’s 5- or 10-year survival with immediate vs delayed treatment and weighs that against their risk for COVID-19 using data from the Johns Hopkins Coronavirus Resource Center.

“We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine.

Spratt explained that almost every organization, professional society, and government has created something like a three-tier system. Tier 1 represents urgent cases and patients who need immediate treatment. For tier 2, treatment can be delayed weeks or a month, and with tier 3, it can be delayed until the pandemic is over or it’s deemed safe.

“[This system] sounds good at first glance, but in cancer, we’re always talking about personalized medicine, and it’s mind-blowing that these tier systems are only based on urgency and prognosis,” he told Medscape Medical News.

Spratt offered an example. Consider a patient with a very aggressive brain tumor ― that patient is in tier 1 and should undergo treatment immediately. But will the treatment actually help? And how helpful would the procedure be if, say, the patient is 80 years old and, if infected, would have a 30% to 50% chance of dying from the coronavirus?

“If the model says this guy has a 5% harm and this one has 30% harm, you can use that to help prioritize,” summarized Spratt.

The app can generate risk estimates for patients living anywhere in the world and has already been accessed by people from 37 countries. However, Spratt cautions that it is primarily “designed and calibrated for the US.

“The estimates are based on very large US registries, and though it’s probably somewhat similar across much of the world, there’s probably certain cancer types that are more region specific ― especially something like stomach cancer or certain types of head and neck cancer in parts of Asia, for example,” he said.

Although the app’s COVID-19 data are specific to the county level in the United States, elsewhere in the world, it is only country specific.

“We’re using the best data we have for coronavirus, but everyone knows we still have large data gaps,” he acknowledged.
 

How Accurate?

Asked to comment on the app, Richard Bleicher, MD, leader of the Breast Cancer Program at Fox Chase Cancer Center, Philadelphia, praised the effort and the goal but had some concerns.

“Several questions arise, most important of which is, How accurate is this, and how has this been validated, if at all ― especially as it is too soon to see the outcomes of patients affected in this pandemic?” he told Medscape Medical News.

“We are imposing delays on a broad scale because of the coronavirus, and we are getting continuously changing data as we test more patients. But both situations are novel and may not be accurately represented by the data being pulled, because the datasets use patients from a few years ago, and confounders in these datasets may not apply to this situation,” Bleicher continued.

Although acknowledging the “value in delineating the risk of dying from cancer vs the risk of dying from the SARS-CoV-2 pandemic,” Bleicher urged caution in using the tool to make individual patient decisions.

“We need to remember that the best of modeling ... can be wildly inaccurate and needs to be validated using patients having the circumstances in question. ... This won’t be possible until long after the pandemic is completed, and so the model’s accuracy remains unknown.”

That sentiment was echoed by Giampaolo Bianchini, MD, head of the Breast Cancer Group, Department of Medical Oncology, Ospedale San Raffaele, in Milan, Italy.

“Arbitrarily postponing and modifying treatment strategies including surgery, radiation therapy, and medical therapy without properly balancing the risk/benefit ratio may lead to significantly worse cancer-related outcomes, which largely exceed the actual risks for COVID,” he wrote in an email.

“The OncCOVID app is a remarkable attempt to fill the gap between perception and estimation,” he said. The app provides side by side the COVID-19 risk estimation and the consequences of arbitrary deviation from the standard of care, observed Bianchini.

However, he pointed out weaknesses, including the fact that the “data generated in literature are not always of high quality and do not take into consideration relevant characteristics of the disease and treatment benefit. It should for sure be used, but then also interpreted with caution.”

Another Italian group responded more positively.

“In our opinion, it could be a useful tool for clinicians,” wrote colleagues Alessio Cortelinni and Giampiero Porzio, both medical oncologists at San Salvatore Hospital and the University of L’Aquila, in Italy. “This Web app might assist clinicians in balancing the risk/benefit ratio of being treated and/or access to the outpatient cancer center for each kind of patient (both early and advanced stages), in order to make a more tailored counseling,” they wrote in an email. “Importantly, the Web app might help those clinicians who work ‘alone,’ in peripheral centers, without resources, colleagues, and multidisciplinary tumor boards on whom they can rely.”

Bleicher, who was involved in the COVID-19 Breast Cancer Consortium’s recommendations for prioritizing breast cancer treatment, summarized that the app “may end up being close or accurate, but we won’t know except in hindsight.”
 

This article first appeared on Medscape.com.

Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic.

In early April, as the COVID-19 surge was bearing down on New York City, those treatment decisions were “a juggling act every single day,” Jonathan Yang, MD, PhD, a radiation oncologist from New York’s Memorial Sloan Kettering Cancer Center, told Medscape Medical News.

Eventually, a glut of guidelines, recommendations, and expert opinions aimed at helping oncologists emerged. The tools help navigate the complicated risk-benefit analysis of their patient’s risk of infection by SARS-CoV-2 and delaying therapy.

Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help?
 

Three-Tier Systems Are Not Very Sophisticated

OncCOVID, a free tool that was launched May 26 by the University of Michigan, allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care.

Combining these personal details with data from the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registry and the National Cancer Database, the Michigan app then estimates a patient’s 5- or 10-year survival with immediate vs delayed treatment and weighs that against their risk for COVID-19 using data from the Johns Hopkins Coronavirus Resource Center.

“We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine.

Spratt explained that almost every organization, professional society, and government has created something like a three-tier system. Tier 1 represents urgent cases and patients who need immediate treatment. For tier 2, treatment can be delayed weeks or a month, and with tier 3, it can be delayed until the pandemic is over or it’s deemed safe.

“[This system] sounds good at first glance, but in cancer, we’re always talking about personalized medicine, and it’s mind-blowing that these tier systems are only based on urgency and prognosis,” he told Medscape Medical News.

Spratt offered an example. Consider a patient with a very aggressive brain tumor ― that patient is in tier 1 and should undergo treatment immediately. But will the treatment actually help? And how helpful would the procedure be if, say, the patient is 80 years old and, if infected, would have a 30% to 50% chance of dying from the coronavirus?

“If the model says this guy has a 5% harm and this one has 30% harm, you can use that to help prioritize,” summarized Spratt.

The app can generate risk estimates for patients living anywhere in the world and has already been accessed by people from 37 countries. However, Spratt cautions that it is primarily “designed and calibrated for the US.

“The estimates are based on very large US registries, and though it’s probably somewhat similar across much of the world, there’s probably certain cancer types that are more region specific ― especially something like stomach cancer or certain types of head and neck cancer in parts of Asia, for example,” he said.

Although the app’s COVID-19 data are specific to the county level in the United States, elsewhere in the world, it is only country specific.

“We’re using the best data we have for coronavirus, but everyone knows we still have large data gaps,” he acknowledged.
 

How Accurate?

Asked to comment on the app, Richard Bleicher, MD, leader of the Breast Cancer Program at Fox Chase Cancer Center, Philadelphia, praised the effort and the goal but had some concerns.

“Several questions arise, most important of which is, How accurate is this, and how has this been validated, if at all ― especially as it is too soon to see the outcomes of patients affected in this pandemic?” he told Medscape Medical News.

“We are imposing delays on a broad scale because of the coronavirus, and we are getting continuously changing data as we test more patients. But both situations are novel and may not be accurately represented by the data being pulled, because the datasets use patients from a few years ago, and confounders in these datasets may not apply to this situation,” Bleicher continued.

Although acknowledging the “value in delineating the risk of dying from cancer vs the risk of dying from the SARS-CoV-2 pandemic,” Bleicher urged caution in using the tool to make individual patient decisions.

“We need to remember that the best of modeling ... can be wildly inaccurate and needs to be validated using patients having the circumstances in question. ... This won’t be possible until long after the pandemic is completed, and so the model’s accuracy remains unknown.”

That sentiment was echoed by Giampaolo Bianchini, MD, head of the Breast Cancer Group, Department of Medical Oncology, Ospedale San Raffaele, in Milan, Italy.

“Arbitrarily postponing and modifying treatment strategies including surgery, radiation therapy, and medical therapy without properly balancing the risk/benefit ratio may lead to significantly worse cancer-related outcomes, which largely exceed the actual risks for COVID,” he wrote in an email.

“The OncCOVID app is a remarkable attempt to fill the gap between perception and estimation,” he said. The app provides side by side the COVID-19 risk estimation and the consequences of arbitrary deviation from the standard of care, observed Bianchini.

However, he pointed out weaknesses, including the fact that the “data generated in literature are not always of high quality and do not take into consideration relevant characteristics of the disease and treatment benefit. It should for sure be used, but then also interpreted with caution.”

Another Italian group responded more positively.

“In our opinion, it could be a useful tool for clinicians,” wrote colleagues Alessio Cortelinni and Giampiero Porzio, both medical oncologists at San Salvatore Hospital and the University of L’Aquila, in Italy. “This Web app might assist clinicians in balancing the risk/benefit ratio of being treated and/or access to the outpatient cancer center for each kind of patient (both early and advanced stages), in order to make a more tailored counseling,” they wrote in an email. “Importantly, the Web app might help those clinicians who work ‘alone,’ in peripheral centers, without resources, colleagues, and multidisciplinary tumor boards on whom they can rely.”

Bleicher, who was involved in the COVID-19 Breast Cancer Consortium’s recommendations for prioritizing breast cancer treatment, summarized that the app “may end up being close or accurate, but we won’t know except in hindsight.”
 

This article first appeared on Medscape.com.