AVAHO

Opioid and nonopioid prescription pain medications have taken different journeys since 2009, but they ended up in the same place in 2018, according to a recent report from the National Center for Health Statistics.

At least by one measure, anyway. Survey data from 2009 to 2010 show that 6.2% of adults aged 20 years and older had taken at least one prescription opioid in the last 30 days and 4.3% had used a prescription nonopioid without an opioid. By 2017-2018, past 30-day use of both drug groups was 5.7%, Craig M. Hales, MD, and associates said in an NCHS data brief.

“Opioids may be prescribed together with nonopioid pain medications, [but] nonpharmacologic and nonopioid-containing pharmacologic therapies are preferred for management of chronic pain,” the NCHS researchers noted.

The increase in prescription nonopioid use over the entire 10-year period managed to reach statistical significance, as did the short-term increase in nonopioids from 2015-2016 to 2017-2018, but the 10-year trend for opioids was not significant, based on data from the National Health and Nutrition Examination Survey.

Much of the analysis focused on 2015-2018, when 30-day use of any prescription pain medication was reported by 10.7% of adults aged 20 years and older, with use of opioids at 5.7% and nonopioids at 5.0%. For women, use of any pain drug was 12.6% (6.4% opioid, 6.2% nonopioid) from 2015 to 2018, compared with 8.7% for men (4.9%, 3.8%), Dr. Hales and associates reported.

Past 30-day use of both opioids and nonopioids over those 4 years was highest for non-Hispanic whites and lowest, by a significant margin for both drug groups, among non-Hispanic Asian adults, a pattern that held for both men and women, they said.

[email protected]

Opioid and nonopioid prescription pain medications have taken different journeys since 2009, but they ended up in the same place in 2018, according to a recent report from the National Center for Health Statistics.

At least by one measure, anyway. Survey data from 2009 to 2010 show that 6.2% of adults aged 20 years and older had taken at least one prescription opioid in the last 30 days and 4.3% had used a prescription nonopioid without an opioid. By 2017-2018, past 30-day use of both drug groups was 5.7%, Craig M. Hales, MD, and associates said in an NCHS data brief.

“Opioids may be prescribed together with nonopioid pain medications, [but] nonpharmacologic and nonopioid-containing pharmacologic therapies are preferred for management of chronic pain,” the NCHS researchers noted.

The increase in prescription nonopioid use over the entire 10-year period managed to reach statistical significance, as did the short-term increase in nonopioids from 2015-2016 to 2017-2018, but the 10-year trend for opioids was not significant, based on data from the National Health and Nutrition Examination Survey.

Much of the analysis focused on 2015-2018, when 30-day use of any prescription pain medication was reported by 10.7% of adults aged 20 years and older, with use of opioids at 5.7% and nonopioids at 5.0%. For women, use of any pain drug was 12.6% (6.4% opioid, 6.2% nonopioid) from 2015 to 2018, compared with 8.7% for men (4.9%, 3.8%), Dr. Hales and associates reported.

Past 30-day use of both opioids and nonopioids over those 4 years was highest for non-Hispanic whites and lowest, by a significant margin for both drug groups, among non-Hispanic Asian adults, a pattern that held for both men and women, they said.

[email protected]

Opioid and nonopioid prescription pain medications have taken different journeys since 2009, but they ended up in the same place in 2018, according to a recent report from the National Center for Health Statistics.

At least by one measure, anyway. Survey data from 2009 to 2010 show that 6.2% of adults aged 20 years and older had taken at least one prescription opioid in the last 30 days and 4.3% had used a prescription nonopioid without an opioid. By 2017-2018, past 30-day use of both drug groups was 5.7%, Craig M. Hales, MD, and associates said in an NCHS data brief.

“Opioids may be prescribed together with nonopioid pain medications, [but] nonpharmacologic and nonopioid-containing pharmacologic therapies are preferred for management of chronic pain,” the NCHS researchers noted.

The increase in prescription nonopioid use over the entire 10-year period managed to reach statistical significance, as did the short-term increase in nonopioids from 2015-2016 to 2017-2018, but the 10-year trend for opioids was not significant, based on data from the National Health and Nutrition Examination Survey.

Much of the analysis focused on 2015-2018, when 30-day use of any prescription pain medication was reported by 10.7% of adults aged 20 years and older, with use of opioids at 5.7% and nonopioids at 5.0%. For women, use of any pain drug was 12.6% (6.4% opioid, 6.2% nonopioid) from 2015 to 2018, compared with 8.7% for men (4.9%, 3.8%), Dr. Hales and associates reported.

Past 30-day use of both opioids and nonopioids over those 4 years was highest for non-Hispanic whites and lowest, by a significant margin for both drug groups, among non-Hispanic Asian adults, a pattern that held for both men and women, they said.

[email protected]

Treating hypertension with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) was associated with a reduced risk for colorectal cancer, according to findings from a large retrospective study.

However, another study reported just over a year ago suggested that ACE inhibitors, but not ARBs, are associated with an increased risk for lung cancer. An expert approached for comment emphasized that both studies are observational, and, as such, they only show an association, not causation.

In this latest study, published online July 6 in the journal Hypertension, the use of ACE inhibitors/ARBs was associated with a 22% lower risk for colorectal cancer developing within 3 years after a negative baseline colonoscopy.

This is the largest study to date, with a cohort of more than 185,000 patients, to suggest a significant protective effect for these two common antihypertensive medications, the authors note. The risk of developing colorectal cancer decreased with longer duration of ACE inhibitor/ARB use, with a 5% reduction in adjusted hazard ratio risk for each year of use. However, this effect was limited to patients who had negative colonoscopies within a 3-year period and did not extend beyond that point.

Lead author Wai K. Leung, MD, clinical professor of medicine at the University of Hong Kong, explained that they are not advising patients to take ACE inhibitors simply to prevent cancer. “Unlike aspirin and statins, the potential chemopreventive role of ACE inhibitors on cancer has never been established,” he said in an interview. “The study findings may favor the use of ACE inhibitors in the treatment of hypertension, over many other antihypertensives, in some patients for preventing colorectal cancer.”

Increased or reduced risk?

There has been considerable debate about the potential carcinogenic effects of ACE inhibitors and ARBs, and the relationship with “various solid organ cancer risks have been unsettled,” the authors note. Studies have produced conflicting results – showing no overall cancer risk and a modestly increased overall cancer risk – associated with these agents.

A recent study reported that ACE inhibitors, as compared with ARBs, increased risk for lung cancer by 14%. The risk for lung cancer increased by 22% among those using ACE inhibitors for 5 years, and the risk peaked at 31% for patients who took ACE inhibitors for 10 years or longer.

The lead author of that lung cancer study, Laurent Azoulay, PhD, of McGill University in Montreal, offered some thoughts on the seemingly conflicting data now being reported showing a reduction in the risk of colorectal cancer.

“In a nutshell, this study has important methodologic issues that can explain the observed findings,” he said in an interview.

Dr. Azoulay pointed out that, in the univariate model, the use of ACE inhibitors/ARBs was associated with a 26% increased risk of colorectal cancer. “It is only after propensity score adjustment that the effect estimate reversed in the protective direction,” he pointed out. “However, the variables included in the propensity score model were measured in the same time window as the exposure, which can lead to an overadjustment bias and generate spurious findings.”

Another issue is that the study period did not begin at the time of the exposure, but rather at a distant point after treatment initiation – in this case, colorectal cancer screening. “As such, the authors excluded patients who were previously diagnosed with colorectal cancer prior to that point, which likely included patients exposed to ACE inhibitors/ARBs,” he said. “This approach can lead to the inclusion of the ‘survivors’ for whom the risk of developing colorectal cancer is lower.

“But certainly,” Dr. Azoulay added, “this possible association should be investigated using methodologically sound approaches.”

Take-home message for physicians

Another expert emphasized the observational nature of both studies. Raymond Townsend, MD, director of the Hypertension Program and a professor of medicine at the Hospital of the University of Pennsylvania, Philadelphia, said: “First and foremost, these are observational studies and cannot make inference about causality; they can only show associations.”

He pointed out that, sometimes, associations are truly present, whereas at other times, there is bias or confounding that cannot be controlled for statistically because it is “unknown.” That said, the size of this latest study is a plus, and there is a reasonable follow-up period.

“The take-home [message] for practitioners is that there may be a benefit in keeping older people on ACE inhibitors on the likelihood of developing colorectal cancer if your last colonoscopy was negative,” Dr. Townsend, who was not involved in the study, said in an interview.

But there are some questions that remain unanswered regarding characteristics of the cohort, Dr. Townsend noted. “Who were the people having the colonoscopy in the first place? Were they a group at higher risk? Why were some on an ACE inhibitors/ARBs and many others not?” 

There are other conclusions that clinicians can glean from this. “Make a choice of treatment for a patient based on your best estimate of what will lower their blood pressure and prevent hypertension-mediated organ damage,” said Dr. Townsend, who is also an American Heart Association volunteer expert. “Keep in mind that patients hear about these studies and read unreviewed blogs on the web and so have questions.”

He emphasized that it always comes back to two things. “One is that every treatment decision is inherently a risk-benefit scenario,” he said. “And second is that most of our patients are adults, and if they choose to not be treated for their hypertension despite our best advice and reasoning with them, relinquish control and let them proceed as they wish, offering to renegotiate in the future when and if they reconsider.”

Study details

In the latest study, Dr. Leung and colleagues conducted a retrospective cohort study and used data from an electronic health care database of the Hong Kong Hospital Authority. A total of 187,897 individuals aged 40 years and older had undergone colonoscopy between 2005 and 2013 with a negative result and were included in the analysis.

The study’s primary outcome was colorectal cancer that was diagnosed between 6 and 36 months after undergoing colonoscopy, and the median age at colonoscopy was 60.6 years. Within this population, 30,856 patients (16.4%) used ACE inhibitors/ARBs.

Between 6 months and 3 years after undergoing colonoscopy, 854 cases of colorectal cancer were diagnosed, with an incidence rate of 15.2 per 10,000 person-years. The median time between colonoscopy and diagnosis was 1.2 years.

ACE inhibitor/ARB users had a median duration of 3.3 years of use within the 5-year period before their colonoscopy. Within this group, there were 169 (0.55%) cases of colorectal cancer. On univariate analysis, the crude hazard ratio (HR) of colorectal cancer and ACE inhibitor/ARB use was 1.26 (P = .008), but on propensity score regression adjustment, the adjusted HR became 0.78.

The propensity score absolute reduction in risk for users was 3.2 per 10,000 person-years versus nonusers, and stratification by subsite showed an HR of 0.77 for distal cancers and 0.83 for proximal cancers.

In a subgroup analysis, the benefits of ACE inhibitors and ARBs were seen in patients aged 55 years or older (adjusted HR, 0.79) and in those with a history of colonic polyps (adjusted HR, 0.71).

The authors also assessed if there was an association between these medications and other types of cancer. On univariate analysis, usage was associated with an increased risk of lung and prostate cancer but lower risk of breast cancer. But after propensity score regression adjustment, the associations were no longer there.

The study was funded by the Health and Medical Research Fund of the Hong Kong SAR Government. Dr. Leung has received honorarium for attending advisory board meetings of AbbVie, Takeda, and Abbott Laboratories; coauthor Esther W. Chan has received funding support from Pfizer, Bristol-Myers Squibb, Bayer, Takeda, Janssen (a division of Johnson & Johnson); Research Grants Council of Hong Kong; Narcotics Division, Security Bureau; and the National Natural Science Foundation of China, all for work unrelated to the current study. None of the other authors have disclosed relevant financial relationships. Dr. Azoulay has disclosed no relevant financial relationships. Dr. Townsend is employed by Penn Medicine.

A version of this article originally appeared on Medscape.com.

Treating hypertension with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) was associated with a reduced risk for colorectal cancer, according to findings from a large retrospective study.

However, another study reported just over a year ago suggested that ACE inhibitors, but not ARBs, are associated with an increased risk for lung cancer. An expert approached for comment emphasized that both studies are observational, and, as such, they only show an association, not causation.

In this latest study, published online July 6 in the journal Hypertension, the use of ACE inhibitors/ARBs was associated with a 22% lower risk for colorectal cancer developing within 3 years after a negative baseline colonoscopy.

This is the largest study to date, with a cohort of more than 185,000 patients, to suggest a significant protective effect for these two common antihypertensive medications, the authors note. The risk of developing colorectal cancer decreased with longer duration of ACE inhibitor/ARB use, with a 5% reduction in adjusted hazard ratio risk for each year of use. However, this effect was limited to patients who had negative colonoscopies within a 3-year period and did not extend beyond that point.

Lead author Wai K. Leung, MD, clinical professor of medicine at the University of Hong Kong, explained that they are not advising patients to take ACE inhibitors simply to prevent cancer. “Unlike aspirin and statins, the potential chemopreventive role of ACE inhibitors on cancer has never been established,” he said in an interview. “The study findings may favor the use of ACE inhibitors in the treatment of hypertension, over many other antihypertensives, in some patients for preventing colorectal cancer.”

Increased or reduced risk?

There has been considerable debate about the potential carcinogenic effects of ACE inhibitors and ARBs, and the relationship with “various solid organ cancer risks have been unsettled,” the authors note. Studies have produced conflicting results – showing no overall cancer risk and a modestly increased overall cancer risk – associated with these agents.

A recent study reported that ACE inhibitors, as compared with ARBs, increased risk for lung cancer by 14%. The risk for lung cancer increased by 22% among those using ACE inhibitors for 5 years, and the risk peaked at 31% for patients who took ACE inhibitors for 10 years or longer.

The lead author of that lung cancer study, Laurent Azoulay, PhD, of McGill University in Montreal, offered some thoughts on the seemingly conflicting data now being reported showing a reduction in the risk of colorectal cancer.

“In a nutshell, this study has important methodologic issues that can explain the observed findings,” he said in an interview.

Dr. Azoulay pointed out that, in the univariate model, the use of ACE inhibitors/ARBs was associated with a 26% increased risk of colorectal cancer. “It is only after propensity score adjustment that the effect estimate reversed in the protective direction,” he pointed out. “However, the variables included in the propensity score model were measured in the same time window as the exposure, which can lead to an overadjustment bias and generate spurious findings.”

Another issue is that the study period did not begin at the time of the exposure, but rather at a distant point after treatment initiation – in this case, colorectal cancer screening. “As such, the authors excluded patients who were previously diagnosed with colorectal cancer prior to that point, which likely included patients exposed to ACE inhibitors/ARBs,” he said. “This approach can lead to the inclusion of the ‘survivors’ for whom the risk of developing colorectal cancer is lower.

“But certainly,” Dr. Azoulay added, “this possible association should be investigated using methodologically sound approaches.”

Take-home message for physicians

Another expert emphasized the observational nature of both studies. Raymond Townsend, MD, director of the Hypertension Program and a professor of medicine at the Hospital of the University of Pennsylvania, Philadelphia, said: “First and foremost, these are observational studies and cannot make inference about causality; they can only show associations.”

He pointed out that, sometimes, associations are truly present, whereas at other times, there is bias or confounding that cannot be controlled for statistically because it is “unknown.” That said, the size of this latest study is a plus, and there is a reasonable follow-up period.

“The take-home [message] for practitioners is that there may be a benefit in keeping older people on ACE inhibitors on the likelihood of developing colorectal cancer if your last colonoscopy was negative,” Dr. Townsend, who was not involved in the study, said in an interview.

But there are some questions that remain unanswered regarding characteristics of the cohort, Dr. Townsend noted. “Who were the people having the colonoscopy in the first place? Were they a group at higher risk? Why were some on an ACE inhibitors/ARBs and many others not?” 

There are other conclusions that clinicians can glean from this. “Make a choice of treatment for a patient based on your best estimate of what will lower their blood pressure and prevent hypertension-mediated organ damage,” said Dr. Townsend, who is also an American Heart Association volunteer expert. “Keep in mind that patients hear about these studies and read unreviewed blogs on the web and so have questions.”

He emphasized that it always comes back to two things. “One is that every treatment decision is inherently a risk-benefit scenario,” he said. “And second is that most of our patients are adults, and if they choose to not be treated for their hypertension despite our best advice and reasoning with them, relinquish control and let them proceed as they wish, offering to renegotiate in the future when and if they reconsider.”

Study details

In the latest study, Dr. Leung and colleagues conducted a retrospective cohort study and used data from an electronic health care database of the Hong Kong Hospital Authority. A total of 187,897 individuals aged 40 years and older had undergone colonoscopy between 2005 and 2013 with a negative result and were included in the analysis.

The study’s primary outcome was colorectal cancer that was diagnosed between 6 and 36 months after undergoing colonoscopy, and the median age at colonoscopy was 60.6 years. Within this population, 30,856 patients (16.4%) used ACE inhibitors/ARBs.

Between 6 months and 3 years after undergoing colonoscopy, 854 cases of colorectal cancer were diagnosed, with an incidence rate of 15.2 per 10,000 person-years. The median time between colonoscopy and diagnosis was 1.2 years.

ACE inhibitor/ARB users had a median duration of 3.3 years of use within the 5-year period before their colonoscopy. Within this group, there were 169 (0.55%) cases of colorectal cancer. On univariate analysis, the crude hazard ratio (HR) of colorectal cancer and ACE inhibitor/ARB use was 1.26 (P = .008), but on propensity score regression adjustment, the adjusted HR became 0.78.

The propensity score absolute reduction in risk for users was 3.2 per 10,000 person-years versus nonusers, and stratification by subsite showed an HR of 0.77 for distal cancers and 0.83 for proximal cancers.

In a subgroup analysis, the benefits of ACE inhibitors and ARBs were seen in patients aged 55 years or older (adjusted HR, 0.79) and in those with a history of colonic polyps (adjusted HR, 0.71).

The authors also assessed if there was an association between these medications and other types of cancer. On univariate analysis, usage was associated with an increased risk of lung and prostate cancer but lower risk of breast cancer. But after propensity score regression adjustment, the associations were no longer there.

The study was funded by the Health and Medical Research Fund of the Hong Kong SAR Government. Dr. Leung has received honorarium for attending advisory board meetings of AbbVie, Takeda, and Abbott Laboratories; coauthor Esther W. Chan has received funding support from Pfizer, Bristol-Myers Squibb, Bayer, Takeda, Janssen (a division of Johnson & Johnson); Research Grants Council of Hong Kong; Narcotics Division, Security Bureau; and the National Natural Science Foundation of China, all for work unrelated to the current study. None of the other authors have disclosed relevant financial relationships. Dr. Azoulay has disclosed no relevant financial relationships. Dr. Townsend is employed by Penn Medicine.

A version of this article originally appeared on Medscape.com.

Treating hypertension with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) was associated with a reduced risk for colorectal cancer, according to findings from a large retrospective study.

However, another study reported just over a year ago suggested that ACE inhibitors, but not ARBs, are associated with an increased risk for lung cancer. An expert approached for comment emphasized that both studies are observational, and, as such, they only show an association, not causation.

In this latest study, published online July 6 in the journal Hypertension, the use of ACE inhibitors/ARBs was associated with a 22% lower risk for colorectal cancer developing within 3 years after a negative baseline colonoscopy.

This is the largest study to date, with a cohort of more than 185,000 patients, to suggest a significant protective effect for these two common antihypertensive medications, the authors note. The risk of developing colorectal cancer decreased with longer duration of ACE inhibitor/ARB use, with a 5% reduction in adjusted hazard ratio risk for each year of use. However, this effect was limited to patients who had negative colonoscopies within a 3-year period and did not extend beyond that point.

Lead author Wai K. Leung, MD, clinical professor of medicine at the University of Hong Kong, explained that they are not advising patients to take ACE inhibitors simply to prevent cancer. “Unlike aspirin and statins, the potential chemopreventive role of ACE inhibitors on cancer has never been established,” he said in an interview. “The study findings may favor the use of ACE inhibitors in the treatment of hypertension, over many other antihypertensives, in some patients for preventing colorectal cancer.”

Increased or reduced risk?

There has been considerable debate about the potential carcinogenic effects of ACE inhibitors and ARBs, and the relationship with “various solid organ cancer risks have been unsettled,” the authors note. Studies have produced conflicting results – showing no overall cancer risk and a modestly increased overall cancer risk – associated with these agents.

A recent study reported that ACE inhibitors, as compared with ARBs, increased risk for lung cancer by 14%. The risk for lung cancer increased by 22% among those using ACE inhibitors for 5 years, and the risk peaked at 31% for patients who took ACE inhibitors for 10 years or longer.

The lead author of that lung cancer study, Laurent Azoulay, PhD, of McGill University in Montreal, offered some thoughts on the seemingly conflicting data now being reported showing a reduction in the risk of colorectal cancer.

“In a nutshell, this study has important methodologic issues that can explain the observed findings,” he said in an interview.

Dr. Azoulay pointed out that, in the univariate model, the use of ACE inhibitors/ARBs was associated with a 26% increased risk of colorectal cancer. “It is only after propensity score adjustment that the effect estimate reversed in the protective direction,” he pointed out. “However, the variables included in the propensity score model were measured in the same time window as the exposure, which can lead to an overadjustment bias and generate spurious findings.”

Another issue is that the study period did not begin at the time of the exposure, but rather at a distant point after treatment initiation – in this case, colorectal cancer screening. “As such, the authors excluded patients who were previously diagnosed with colorectal cancer prior to that point, which likely included patients exposed to ACE inhibitors/ARBs,” he said. “This approach can lead to the inclusion of the ‘survivors’ for whom the risk of developing colorectal cancer is lower.

“But certainly,” Dr. Azoulay added, “this possible association should be investigated using methodologically sound approaches.”

Take-home message for physicians

Another expert emphasized the observational nature of both studies. Raymond Townsend, MD, director of the Hypertension Program and a professor of medicine at the Hospital of the University of Pennsylvania, Philadelphia, said: “First and foremost, these are observational studies and cannot make inference about causality; they can only show associations.”

He pointed out that, sometimes, associations are truly present, whereas at other times, there is bias or confounding that cannot be controlled for statistically because it is “unknown.” That said, the size of this latest study is a plus, and there is a reasonable follow-up period.

“The take-home [message] for practitioners is that there may be a benefit in keeping older people on ACE inhibitors on the likelihood of developing colorectal cancer if your last colonoscopy was negative,” Dr. Townsend, who was not involved in the study, said in an interview.

But there are some questions that remain unanswered regarding characteristics of the cohort, Dr. Townsend noted. “Who were the people having the colonoscopy in the first place? Were they a group at higher risk? Why were some on an ACE inhibitors/ARBs and many others not?” 

There are other conclusions that clinicians can glean from this. “Make a choice of treatment for a patient based on your best estimate of what will lower their blood pressure and prevent hypertension-mediated organ damage,” said Dr. Townsend, who is also an American Heart Association volunteer expert. “Keep in mind that patients hear about these studies and read unreviewed blogs on the web and so have questions.”

He emphasized that it always comes back to two things. “One is that every treatment decision is inherently a risk-benefit scenario,” he said. “And second is that most of our patients are adults, and if they choose to not be treated for their hypertension despite our best advice and reasoning with them, relinquish control and let them proceed as they wish, offering to renegotiate in the future when and if they reconsider.”

Study details

In the latest study, Dr. Leung and colleagues conducted a retrospective cohort study and used data from an electronic health care database of the Hong Kong Hospital Authority. A total of 187,897 individuals aged 40 years and older had undergone colonoscopy between 2005 and 2013 with a negative result and were included in the analysis.

The study’s primary outcome was colorectal cancer that was diagnosed between 6 and 36 months after undergoing colonoscopy, and the median age at colonoscopy was 60.6 years. Within this population, 30,856 patients (16.4%) used ACE inhibitors/ARBs.

Between 6 months and 3 years after undergoing colonoscopy, 854 cases of colorectal cancer were diagnosed, with an incidence rate of 15.2 per 10,000 person-years. The median time between colonoscopy and diagnosis was 1.2 years.

ACE inhibitor/ARB users had a median duration of 3.3 years of use within the 5-year period before their colonoscopy. Within this group, there were 169 (0.55%) cases of colorectal cancer. On univariate analysis, the crude hazard ratio (HR) of colorectal cancer and ACE inhibitor/ARB use was 1.26 (P = .008), but on propensity score regression adjustment, the adjusted HR became 0.78.

The propensity score absolute reduction in risk for users was 3.2 per 10,000 person-years versus nonusers, and stratification by subsite showed an HR of 0.77 for distal cancers and 0.83 for proximal cancers.

In a subgroup analysis, the benefits of ACE inhibitors and ARBs were seen in patients aged 55 years or older (adjusted HR, 0.79) and in those with a history of colonic polyps (adjusted HR, 0.71).

The authors also assessed if there was an association between these medications and other types of cancer. On univariate analysis, usage was associated with an increased risk of lung and prostate cancer but lower risk of breast cancer. But after propensity score regression adjustment, the associations were no longer there.

The study was funded by the Health and Medical Research Fund of the Hong Kong SAR Government. Dr. Leung has received honorarium for attending advisory board meetings of AbbVie, Takeda, and Abbott Laboratories; coauthor Esther W. Chan has received funding support from Pfizer, Bristol-Myers Squibb, Bayer, Takeda, Janssen (a division of Johnson & Johnson); Research Grants Council of Hong Kong; Narcotics Division, Security Bureau; and the National Natural Science Foundation of China, all for work unrelated to the current study. None of the other authors have disclosed relevant financial relationships. Dr. Azoulay has disclosed no relevant financial relationships. Dr. Townsend is employed by Penn Medicine.

A version of this article originally appeared on Medscape.com.

Lipophilic statin use is associated with reduced mortality risk in women with ovarian cancer, findings from a large observational study suggest.

The study included 10,062 patients with epithelial ovarian cancer enrolled in the Finnish national cancer registry. There were 2,621 patients who were prescribed statins between 1995 and 2015, and 80% of them used lipophilic statins.

When compared with no statin use, any statin use was associated with a 40% reduction in ovarian cancer mortality (weighted hazard ratio, 0.60), and any use of lipophilic statins was associated with a 43% reduction in ovarian cancer mortality (wHR, 0.57).

Kala Visvanathan, MD, of Johns Hopkins University in Baltimore, and colleagues reported these findings in a poster at the AACR virtual meeting II.

Reductions in ovarian cancer mortality were observed in women who took simvastatin or atorvastatin (wHRs 0.24 and 0.20, respectively), the researchers found.

Lipophilic statin use also was associated with a reduction in ovarian cancer mortality across disease subtypes, although the magnitude of reduction varied. The hazard ratios were 0.60 for high-grade serous ovarian cancer, 0.50 for endometrioid ovarian cancer, 0.20 for clear cell ovarian cancer, 0.30 for mucinous ovarian cancer, and 0.27 for borderline disease.

Survival benefits were evident both in patients who started statins prior to their ovarian cancer diagnosis and in those who started statins after diagnosis.

Never-statin users had a median age of 62 years at baseline, and ever-statin users had a median age of 67 years. The median follow-up was 3.6 years and 5.5 years, respectively.

Data from the registry were linked to prescription claims, and a series of analyses were conducted to examine the association between pre- and postdiagnostic statin use and mortality. The findings were adjusted for age at diagnosis, stage, ovarian cancer subtype, treatments, year of diagnosis, and chronic disease medications. Adherence to statins was greater than 90%.
 

Implications and next steps

The idea of using statins for the treatment of ovarian cancer is appealing because of the promising survival data as well as the broad access, low cost, and tolerability of statins, Dr. Visvanathan said in a statement. About 28% of U.S. adults over age 40 routinely take statins for cholesterol control, and statins are widely used in other countries, she said.

“Our results support research to evaluate the repurposing of therapies that are well tolerated and inexpensive in order to help reduce the global cancer burden,” Dr. Visvanathan and colleagues wrote in their poster.

“Our results provide evidence in support of the evaluation of lipophilic statins, particularly atorvastatin and/or simvastatin, for the treatment of [epithelial ovarian cancer] in conjunction with existing therapies,” the researchers wrote. They added that these statins should be “evaluated in randomized clinical trials that include correlative endpoints.”

Further, the researchers argued that “the results are biologically plausible based on known mechanisms associated with statin use and highlight the fact that statins may be effective to treat more than one disease/outcome (i.e., high cholesterol, EOC [epithelial ovarian cancer], breast cancer).”

The results of this study are intriguing, according to James Yarmolinsky, MSc, of the University of Bristol, England. Mr. Yarmolinsky is the lead author of a case-control study that showed an association between genetically proxied 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition and lower odds of developing epithelial ovarian cancer (JAMA. 2020;323[7]:646-655).

Mr. Yarmolinsky and colleagues found that HMG-CoA reductase inhibition equivalent to a 38.7-mg/dL reduction in low-density lipoprotein cholesterol was significantly associated with lower odds of epithelial ovarian cancer in the general population (odds ratio, 0.60) and among BRCA1/2 mutation carriers (hazard ratio, 0.69). The findings raised questions about whether a similar association would be seen with medications such as statins that inhibit HMG-CoA reductase.

“These findings linking statin use to lower ovarian cancer mortality are really interesting given our own research suggesting that these drugs may also lower women’s risk of developing this disease in the first place,” Mr. Yarmolinsky said.

“The survival rate for ovarian cancer remains the lowest among all gynecological cancers in the United States, so use of these medications in either a preventive or therapeutic context could offer an important approach for reducing disease burden,” he added. “If the findings reported by Visvanathan and colleagues can be shown to replicate in other large population-based studies, testing the efficacy of statins in a randomized clinical trial could provide definitive evidence of whether these medications lower ovarian cancer mortality.”

The Department of Defense and the Breast Cancer Research Foundation funded the current study. Dr. Visvanathan and Mr. Yarmolinsky reported no disclosures.

[email protected]

SOURCE: Visvanathan K et al. AACR 2020, Abstract 5782.

Lipophilic statin use is associated with reduced mortality risk in women with ovarian cancer, findings from a large observational study suggest.

The study included 10,062 patients with epithelial ovarian cancer enrolled in the Finnish national cancer registry. There were 2,621 patients who were prescribed statins between 1995 and 2015, and 80% of them used lipophilic statins.

When compared with no statin use, any statin use was associated with a 40% reduction in ovarian cancer mortality (weighted hazard ratio, 0.60), and any use of lipophilic statins was associated with a 43% reduction in ovarian cancer mortality (wHR, 0.57).

Kala Visvanathan, MD, of Johns Hopkins University in Baltimore, and colleagues reported these findings in a poster at the AACR virtual meeting II.

Reductions in ovarian cancer mortality were observed in women who took simvastatin or atorvastatin (wHRs 0.24 and 0.20, respectively), the researchers found.

Lipophilic statin use also was associated with a reduction in ovarian cancer mortality across disease subtypes, although the magnitude of reduction varied. The hazard ratios were 0.60 for high-grade serous ovarian cancer, 0.50 for endometrioid ovarian cancer, 0.20 for clear cell ovarian cancer, 0.30 for mucinous ovarian cancer, and 0.27 for borderline disease.

Survival benefits were evident both in patients who started statins prior to their ovarian cancer diagnosis and in those who started statins after diagnosis.

Never-statin users had a median age of 62 years at baseline, and ever-statin users had a median age of 67 years. The median follow-up was 3.6 years and 5.5 years, respectively.

Data from the registry were linked to prescription claims, and a series of analyses were conducted to examine the association between pre- and postdiagnostic statin use and mortality. The findings were adjusted for age at diagnosis, stage, ovarian cancer subtype, treatments, year of diagnosis, and chronic disease medications. Adherence to statins was greater than 90%.
 

Implications and next steps

The idea of using statins for the treatment of ovarian cancer is appealing because of the promising survival data as well as the broad access, low cost, and tolerability of statins, Dr. Visvanathan said in a statement. About 28% of U.S. adults over age 40 routinely take statins for cholesterol control, and statins are widely used in other countries, she said.

“Our results support research to evaluate the repurposing of therapies that are well tolerated and inexpensive in order to help reduce the global cancer burden,” Dr. Visvanathan and colleagues wrote in their poster.

“Our results provide evidence in support of the evaluation of lipophilic statins, particularly atorvastatin and/or simvastatin, for the treatment of [epithelial ovarian cancer] in conjunction with existing therapies,” the researchers wrote. They added that these statins should be “evaluated in randomized clinical trials that include correlative endpoints.”

Further, the researchers argued that “the results are biologically plausible based on known mechanisms associated with statin use and highlight the fact that statins may be effective to treat more than one disease/outcome (i.e., high cholesterol, EOC [epithelial ovarian cancer], breast cancer).”

The results of this study are intriguing, according to James Yarmolinsky, MSc, of the University of Bristol, England. Mr. Yarmolinsky is the lead author of a case-control study that showed an association between genetically proxied 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition and lower odds of developing epithelial ovarian cancer (JAMA. 2020;323[7]:646-655).

Mr. Yarmolinsky and colleagues found that HMG-CoA reductase inhibition equivalent to a 38.7-mg/dL reduction in low-density lipoprotein cholesterol was significantly associated with lower odds of epithelial ovarian cancer in the general population (odds ratio, 0.60) and among BRCA1/2 mutation carriers (hazard ratio, 0.69). The findings raised questions about whether a similar association would be seen with medications such as statins that inhibit HMG-CoA reductase.

“These findings linking statin use to lower ovarian cancer mortality are really interesting given our own research suggesting that these drugs may also lower women’s risk of developing this disease in the first place,” Mr. Yarmolinsky said.

“The survival rate for ovarian cancer remains the lowest among all gynecological cancers in the United States, so use of these medications in either a preventive or therapeutic context could offer an important approach for reducing disease burden,” he added. “If the findings reported by Visvanathan and colleagues can be shown to replicate in other large population-based studies, testing the efficacy of statins in a randomized clinical trial could provide definitive evidence of whether these medications lower ovarian cancer mortality.”

The Department of Defense and the Breast Cancer Research Foundation funded the current study. Dr. Visvanathan and Mr. Yarmolinsky reported no disclosures.

[email protected]

SOURCE: Visvanathan K et al. AACR 2020, Abstract 5782.

Lipophilic statin use is associated with reduced mortality risk in women with ovarian cancer, findings from a large observational study suggest.

The study included 10,062 patients with epithelial ovarian cancer enrolled in the Finnish national cancer registry. There were 2,621 patients who were prescribed statins between 1995 and 2015, and 80% of them used lipophilic statins.

When compared with no statin use, any statin use was associated with a 40% reduction in ovarian cancer mortality (weighted hazard ratio, 0.60), and any use of lipophilic statins was associated with a 43% reduction in ovarian cancer mortality (wHR, 0.57).

Kala Visvanathan, MD, of Johns Hopkins University in Baltimore, and colleagues reported these findings in a poster at the AACR virtual meeting II.

Reductions in ovarian cancer mortality were observed in women who took simvastatin or atorvastatin (wHRs 0.24 and 0.20, respectively), the researchers found.

Lipophilic statin use also was associated with a reduction in ovarian cancer mortality across disease subtypes, although the magnitude of reduction varied. The hazard ratios were 0.60 for high-grade serous ovarian cancer, 0.50 for endometrioid ovarian cancer, 0.20 for clear cell ovarian cancer, 0.30 for mucinous ovarian cancer, and 0.27 for borderline disease.

Survival benefits were evident both in patients who started statins prior to their ovarian cancer diagnosis and in those who started statins after diagnosis.

Never-statin users had a median age of 62 years at baseline, and ever-statin users had a median age of 67 years. The median follow-up was 3.6 years and 5.5 years, respectively.

Data from the registry were linked to prescription claims, and a series of analyses were conducted to examine the association between pre- and postdiagnostic statin use and mortality. The findings were adjusted for age at diagnosis, stage, ovarian cancer subtype, treatments, year of diagnosis, and chronic disease medications. Adherence to statins was greater than 90%.
 

Implications and next steps

The idea of using statins for the treatment of ovarian cancer is appealing because of the promising survival data as well as the broad access, low cost, and tolerability of statins, Dr. Visvanathan said in a statement. About 28% of U.S. adults over age 40 routinely take statins for cholesterol control, and statins are widely used in other countries, she said.

“Our results support research to evaluate the repurposing of therapies that are well tolerated and inexpensive in order to help reduce the global cancer burden,” Dr. Visvanathan and colleagues wrote in their poster.

“Our results provide evidence in support of the evaluation of lipophilic statins, particularly atorvastatin and/or simvastatin, for the treatment of [epithelial ovarian cancer] in conjunction with existing therapies,” the researchers wrote. They added that these statins should be “evaluated in randomized clinical trials that include correlative endpoints.”

Further, the researchers argued that “the results are biologically plausible based on known mechanisms associated with statin use and highlight the fact that statins may be effective to treat more than one disease/outcome (i.e., high cholesterol, EOC [epithelial ovarian cancer], breast cancer).”

The results of this study are intriguing, according to James Yarmolinsky, MSc, of the University of Bristol, England. Mr. Yarmolinsky is the lead author of a case-control study that showed an association between genetically proxied 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition and lower odds of developing epithelial ovarian cancer (JAMA. 2020;323[7]:646-655).

Mr. Yarmolinsky and colleagues found that HMG-CoA reductase inhibition equivalent to a 38.7-mg/dL reduction in low-density lipoprotein cholesterol was significantly associated with lower odds of epithelial ovarian cancer in the general population (odds ratio, 0.60) and among BRCA1/2 mutation carriers (hazard ratio, 0.69). The findings raised questions about whether a similar association would be seen with medications such as statins that inhibit HMG-CoA reductase.

“These findings linking statin use to lower ovarian cancer mortality are really interesting given our own research suggesting that these drugs may also lower women’s risk of developing this disease in the first place,” Mr. Yarmolinsky said.

“The survival rate for ovarian cancer remains the lowest among all gynecological cancers in the United States, so use of these medications in either a preventive or therapeutic context could offer an important approach for reducing disease burden,” he added. “If the findings reported by Visvanathan and colleagues can be shown to replicate in other large population-based studies, testing the efficacy of statins in a randomized clinical trial could provide definitive evidence of whether these medications lower ovarian cancer mortality.”

The Department of Defense and the Breast Cancer Research Foundation funded the current study. Dr. Visvanathan and Mr. Yarmolinsky reported no disclosures.

[email protected]

SOURCE: Visvanathan K et al. AACR 2020, Abstract 5782.

The definition of stage IV renal cell carcinoma (RCC) should be expanded to include lymph node–positive stage III disease, according to a population-level cohort study published in Cancer.

While patients with lymph node–negative stage III disease had superior overall survival at 5 years, survival rates were similar between patients with node–positive stage III disease and stage IV disease. This supports reclassifying stage III node-positive RCC to stage IV, according to researchers.

“Prior institutional studies have indicated that, among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease,” wrote Arnav Srivastava, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and colleagues.

The researchers used data from the National Cancer Database to identify patients with AJCC stage III or stage IV RCC who had undergone nephrectomy and lymph node dissection.

The cohort included 8,988 patients, 6,587 of whom had node–negative stage III disease, 2,218 of whom had node–positive stage III disease, and 183 of whom had stage IV metastatic disease. The researchers compared relative survival between staging groups.

The 5-year overall survival rate was 61.9% in patients with node–negative stage III RCC (95% confidence interval, 60.3%-63.4%), 22.7% in patients with node-positive stage III RCC (95% CI, 20.6%-24.9%), and 15.6% in patients with stage IV RCC (95% CI, 11.1%-23.8%).

“Patients with lymph node–positive stage III disease and those with stage IV disease were found to have overlapping 95% CIs when measuring 5-year survival; both demonstrated similar mortality,” the researchers reported. They further noted that these findings remained unchanged when patients were stratified by clear cell and non–clear cell histology.

In an accompanying editorial, Daniel D. Shapiro, MD, of the University of Texas MD Anderson Cancer Center, Houston, and E. Jason Abel, MD, of the University of Wisconsin–Madison, said the study results suggest the clinical phenotype of patients with isolated lymph node metastases is different from other stage III RCCs.

“Future editions of the AJCC staging system [should] recognize the increased risk with [lymph node–positive stage III] tumors and consider reclassification of [these] tumors as stage IV tumors so that baseline risks are more accurately measured in these rare populations,” they recommended.

Dr. Srivastava and colleagues acknowledged that two key limitations of the study were the retrospective design and the absence of data on other survival measures, such as metastasis-free and cancer-specific survival.

“Despite these limitations, we believe the current study was able to significantly build on prior work recommending the reclassification of lymph node–positive RCC as stage IV cancer,” they concluded.

The National Cancer Institute supported the study. Some study authors disclosed relationships with pharmaceutical companies and other organizations for work performed outside of the current study. The editorial authors disclosed no conflicts of interest.

SOURCE: Srivastava A et al. Cancer. 2020 Jul 1;126(13):2991-3001.

The definition of stage IV renal cell carcinoma (RCC) should be expanded to include lymph node–positive stage III disease, according to a population-level cohort study published in Cancer.

While patients with lymph node–negative stage III disease had superior overall survival at 5 years, survival rates were similar between patients with node–positive stage III disease and stage IV disease. This supports reclassifying stage III node-positive RCC to stage IV, according to researchers.

“Prior institutional studies have indicated that, among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease,” wrote Arnav Srivastava, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and colleagues.

The researchers used data from the National Cancer Database to identify patients with AJCC stage III or stage IV RCC who had undergone nephrectomy and lymph node dissection.

The cohort included 8,988 patients, 6,587 of whom had node–negative stage III disease, 2,218 of whom had node–positive stage III disease, and 183 of whom had stage IV metastatic disease. The researchers compared relative survival between staging groups.

The 5-year overall survival rate was 61.9% in patients with node–negative stage III RCC (95% confidence interval, 60.3%-63.4%), 22.7% in patients with node-positive stage III RCC (95% CI, 20.6%-24.9%), and 15.6% in patients with stage IV RCC (95% CI, 11.1%-23.8%).

“Patients with lymph node–positive stage III disease and those with stage IV disease were found to have overlapping 95% CIs when measuring 5-year survival; both demonstrated similar mortality,” the researchers reported. They further noted that these findings remained unchanged when patients were stratified by clear cell and non–clear cell histology.

In an accompanying editorial, Daniel D. Shapiro, MD, of the University of Texas MD Anderson Cancer Center, Houston, and E. Jason Abel, MD, of the University of Wisconsin–Madison, said the study results suggest the clinical phenotype of patients with isolated lymph node metastases is different from other stage III RCCs.

“Future editions of the AJCC staging system [should] recognize the increased risk with [lymph node–positive stage III] tumors and consider reclassification of [these] tumors as stage IV tumors so that baseline risks are more accurately measured in these rare populations,” they recommended.

Dr. Srivastava and colleagues acknowledged that two key limitations of the study were the retrospective design and the absence of data on other survival measures, such as metastasis-free and cancer-specific survival.

“Despite these limitations, we believe the current study was able to significantly build on prior work recommending the reclassification of lymph node–positive RCC as stage IV cancer,” they concluded.

The National Cancer Institute supported the study. Some study authors disclosed relationships with pharmaceutical companies and other organizations for work performed outside of the current study. The editorial authors disclosed no conflicts of interest.

SOURCE: Srivastava A et al. Cancer. 2020 Jul 1;126(13):2991-3001.

The definition of stage IV renal cell carcinoma (RCC) should be expanded to include lymph node–positive stage III disease, according to a population-level cohort study published in Cancer.

While patients with lymph node–negative stage III disease had superior overall survival at 5 years, survival rates were similar between patients with node–positive stage III disease and stage IV disease. This supports reclassifying stage III node-positive RCC to stage IV, according to researchers.

“Prior institutional studies have indicated that, among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease,” wrote Arnav Srivastava, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and colleagues.

The researchers used data from the National Cancer Database to identify patients with AJCC stage III or stage IV RCC who had undergone nephrectomy and lymph node dissection.

The cohort included 8,988 patients, 6,587 of whom had node–negative stage III disease, 2,218 of whom had node–positive stage III disease, and 183 of whom had stage IV metastatic disease. The researchers compared relative survival between staging groups.

The 5-year overall survival rate was 61.9% in patients with node–negative stage III RCC (95% confidence interval, 60.3%-63.4%), 22.7% in patients with node-positive stage III RCC (95% CI, 20.6%-24.9%), and 15.6% in patients with stage IV RCC (95% CI, 11.1%-23.8%).

“Patients with lymph node–positive stage III disease and those with stage IV disease were found to have overlapping 95% CIs when measuring 5-year survival; both demonstrated similar mortality,” the researchers reported. They further noted that these findings remained unchanged when patients were stratified by clear cell and non–clear cell histology.

In an accompanying editorial, Daniel D. Shapiro, MD, of the University of Texas MD Anderson Cancer Center, Houston, and E. Jason Abel, MD, of the University of Wisconsin–Madison, said the study results suggest the clinical phenotype of patients with isolated lymph node metastases is different from other stage III RCCs.

“Future editions of the AJCC staging system [should] recognize the increased risk with [lymph node–positive stage III] tumors and consider reclassification of [these] tumors as stage IV tumors so that baseline risks are more accurately measured in these rare populations,” they recommended.

Dr. Srivastava and colleagues acknowledged that two key limitations of the study were the retrospective design and the absence of data on other survival measures, such as metastasis-free and cancer-specific survival.

“Despite these limitations, we believe the current study was able to significantly build on prior work recommending the reclassification of lymph node–positive RCC as stage IV cancer,” they concluded.

The National Cancer Institute supported the study. Some study authors disclosed relationships with pharmaceutical companies and other organizations for work performed outside of the current study. The editorial authors disclosed no conflicts of interest.

SOURCE: Srivastava A et al. Cancer. 2020 Jul 1;126(13):2991-3001.

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

Despite a lack of financial penalties, the U.S. Veterans Affairs Health Care System has seen a steady 15% reduction in 30-day all-cause readmissions for patients admitted for heart failure, with no concurrent increase in 30-day mortality, a large cohort study suggests.

Unlike the Center for Medicare & Medicaid’s Hospital Readmissions Reduction Program (HRRP), whose primary objective is reducing payments to hospitals with excess readmissions, the VA’s efforts to reduce readmissions across their system did not include any financial penalties.

“The intervention focused on encouraging participation in transitions of care programs, such as the American College of Cardiology’s Hospital to Home Initiative and the creation of a heart failure provider network that included more than 900 heart failure providers throughout the VA system,” said the study’s lead author Justin T. Parizo, MD, of Stanford (Calif.) University.

The only measuring sticks the VA used were the public reporting of 30-day readmission rates (starting in 2012) and inclusion of those rates into hospitals’ overall star ratings (starting in 2014).  

“The readmissions reductions we saw were similar in magnitude to those seen in patients in CMS fee-for-service categories in the HRRP,” said Dr. Parizo. “And while we had no ability to evaluate causality here, our best guess from what we can see is that there’s been no impact of the readmissions program on mortality,” he added.

Their results were published online June 17 in JAMA Cardiology.

Dr. Parizo and colleagues conducted a cohort study of 304,374 heart failure hospital admissions in 164,566 patients from January 2007 to September 2017. Importantly, he stressed, the researchers were able to do sophisticated risk adjustment for illness trends, something that has been a sticking point in some of the HRRP studies to date.

“We leveraged the robust dataset that the VA provides to adjust for illness severity. Accounting for clinical factors, like blood pressure, weight, creatinine, BNP [B-type natriuretic peptide], and other markers of heart failure severity, but also for changes in coding,” said Dr. Parizo.

Stratification according to left ventricular ejection fraction (LVEF) showed similar results both in terms of 30-day readmission and 30-day mortality for those with LVEF of 40% or greater and those with LVEF less than 40%.

In an interview, Dr. Parizo noted that they actually saw a small but significant uptick in mortality in the 2011-2012 period (compared with 2007-2008) that remains unexplained. “By the 2015-2017 period, 30-day death had returned to baseline levels,” he said.

In contrast, the HRRP, which was rolled out in 2012, has also been shown to reduce readmissions but, in most studies, 30-day mortality had gone up.

“The VA has a very robust quality infrastructure and a robust mechanism for prioritizing certain quality-improvement goals and getting them accomplished that I think they are underrecognized for,” said Leora Horwitz, MD, MHS, the director of the Center for Healthcare Innovation and Delivery Science at NYU Langone Medical Center, New York.

In an interview, she also noted some concern with the uptick seen in the 2011-2012 period, noting that the increase might be the same signal seen with the HRRP intervention.

“This is around the same time period where other people were writing the HRRP papers that showed an increase in mortality, so that’s something to consider,” she said.

Dr. Horwitz coauthored a study published in 2017 indicating that, on a hospital level (compared with a patient level, the approach most other studies took), reductions in readmissions were only weakly correlated with 30-day mortality rates after discharge.

“So, if you think that a hospital that’s behaving badly and keeping people out of the hospital inappropriately to cut down their readmissions, you’d expect to see increased mortality in that hospital, and in our study there was no correlation whatsoever. So there is still debate as to what is behind the increase in mortality on a patient level with heart failure that we’ve seen in some studies,” she said.

Dr. Horwitz doubts an intervention such as the one undertaken in the VA system – even with its fairly soft-touch “name and shame” component – would work in the non-VA hospital world.

“Those who have been in favor of financial penalties have pointed to the fact that, in general, it’s hard to get health systems to respond without financial alignment, even if it’s not an overt financial incentive,” she said.

“The VA is a unique environment,” she noted. “They have a very strong top-down command control focus where people are kind of used to being told, ‘OK, here are the measures we have to address this year.’ It’s good to see that the system that has worked for them for other outcomes also worked for them for heart failure readmissions too.”

Dr. Parizo has disclosed no relevant financial relationships. Dr. Horwitz has worked under contract to Medicare to develop readmission measures. 

A version of this article originally appeared on Medscape.com.

Despite a lack of financial penalties, the U.S. Veterans Affairs Health Care System has seen a steady 15% reduction in 30-day all-cause readmissions for patients admitted for heart failure, with no concurrent increase in 30-day mortality, a large cohort study suggests.

Unlike the Center for Medicare & Medicaid’s Hospital Readmissions Reduction Program (HRRP), whose primary objective is reducing payments to hospitals with excess readmissions, the VA’s efforts to reduce readmissions across their system did not include any financial penalties.

“The intervention focused on encouraging participation in transitions of care programs, such as the American College of Cardiology’s Hospital to Home Initiative and the creation of a heart failure provider network that included more than 900 heart failure providers throughout the VA system,” said the study’s lead author Justin T. Parizo, MD, of Stanford (Calif.) University.

The only measuring sticks the VA used were the public reporting of 30-day readmission rates (starting in 2012) and inclusion of those rates into hospitals’ overall star ratings (starting in 2014).  

“The readmissions reductions we saw were similar in magnitude to those seen in patients in CMS fee-for-service categories in the HRRP,” said Dr. Parizo. “And while we had no ability to evaluate causality here, our best guess from what we can see is that there’s been no impact of the readmissions program on mortality,” he added.

Their results were published online June 17 in JAMA Cardiology.

Dr. Parizo and colleagues conducted a cohort study of 304,374 heart failure hospital admissions in 164,566 patients from January 2007 to September 2017. Importantly, he stressed, the researchers were able to do sophisticated risk adjustment for illness trends, something that has been a sticking point in some of the HRRP studies to date.

“We leveraged the robust dataset that the VA provides to adjust for illness severity. Accounting for clinical factors, like blood pressure, weight, creatinine, BNP [B-type natriuretic peptide], and other markers of heart failure severity, but also for changes in coding,” said Dr. Parizo.

Stratification according to left ventricular ejection fraction (LVEF) showed similar results both in terms of 30-day readmission and 30-day mortality for those with LVEF of 40% or greater and those with LVEF less than 40%.

In an interview, Dr. Parizo noted that they actually saw a small but significant uptick in mortality in the 2011-2012 period (compared with 2007-2008) that remains unexplained. “By the 2015-2017 period, 30-day death had returned to baseline levels,” he said.

In contrast, the HRRP, which was rolled out in 2012, has also been shown to reduce readmissions but, in most studies, 30-day mortality had gone up.

“The VA has a very robust quality infrastructure and a robust mechanism for prioritizing certain quality-improvement goals and getting them accomplished that I think they are underrecognized for,” said Leora Horwitz, MD, MHS, the director of the Center for Healthcare Innovation and Delivery Science at NYU Langone Medical Center, New York.

In an interview, she also noted some concern with the uptick seen in the 2011-2012 period, noting that the increase might be the same signal seen with the HRRP intervention.

“This is around the same time period where other people were writing the HRRP papers that showed an increase in mortality, so that’s something to consider,” she said.

Dr. Horwitz coauthored a study published in 2017 indicating that, on a hospital level (compared with a patient level, the approach most other studies took), reductions in readmissions were only weakly correlated with 30-day mortality rates after discharge.

“So, if you think that a hospital that’s behaving badly and keeping people out of the hospital inappropriately to cut down their readmissions, you’d expect to see increased mortality in that hospital, and in our study there was no correlation whatsoever. So there is still debate as to what is behind the increase in mortality on a patient level with heart failure that we’ve seen in some studies,” she said.

Dr. Horwitz doubts an intervention such as the one undertaken in the VA system – even with its fairly soft-touch “name and shame” component – would work in the non-VA hospital world.

“Those who have been in favor of financial penalties have pointed to the fact that, in general, it’s hard to get health systems to respond without financial alignment, even if it’s not an overt financial incentive,” she said.

“The VA is a unique environment,” she noted. “They have a very strong top-down command control focus where people are kind of used to being told, ‘OK, here are the measures we have to address this year.’ It’s good to see that the system that has worked for them for other outcomes also worked for them for heart failure readmissions too.”

Dr. Parizo has disclosed no relevant financial relationships. Dr. Horwitz has worked under contract to Medicare to develop readmission measures. 

A version of this article originally appeared on Medscape.com.

Despite a lack of financial penalties, the U.S. Veterans Affairs Health Care System has seen a steady 15% reduction in 30-day all-cause readmissions for patients admitted for heart failure, with no concurrent increase in 30-day mortality, a large cohort study suggests.

Unlike the Center for Medicare & Medicaid’s Hospital Readmissions Reduction Program (HRRP), whose primary objective is reducing payments to hospitals with excess readmissions, the VA’s efforts to reduce readmissions across their system did not include any financial penalties.

“The intervention focused on encouraging participation in transitions of care programs, such as the American College of Cardiology’s Hospital to Home Initiative and the creation of a heart failure provider network that included more than 900 heart failure providers throughout the VA system,” said the study’s lead author Justin T. Parizo, MD, of Stanford (Calif.) University.

The only measuring sticks the VA used were the public reporting of 30-day readmission rates (starting in 2012) and inclusion of those rates into hospitals’ overall star ratings (starting in 2014).  

“The readmissions reductions we saw were similar in magnitude to those seen in patients in CMS fee-for-service categories in the HRRP,” said Dr. Parizo. “And while we had no ability to evaluate causality here, our best guess from what we can see is that there’s been no impact of the readmissions program on mortality,” he added.

Their results were published online June 17 in JAMA Cardiology.

Dr. Parizo and colleagues conducted a cohort study of 304,374 heart failure hospital admissions in 164,566 patients from January 2007 to September 2017. Importantly, he stressed, the researchers were able to do sophisticated risk adjustment for illness trends, something that has been a sticking point in some of the HRRP studies to date.

“We leveraged the robust dataset that the VA provides to adjust for illness severity. Accounting for clinical factors, like blood pressure, weight, creatinine, BNP [B-type natriuretic peptide], and other markers of heart failure severity, but also for changes in coding,” said Dr. Parizo.

Stratification according to left ventricular ejection fraction (LVEF) showed similar results both in terms of 30-day readmission and 30-day mortality for those with LVEF of 40% or greater and those with LVEF less than 40%.

In an interview, Dr. Parizo noted that they actually saw a small but significant uptick in mortality in the 2011-2012 period (compared with 2007-2008) that remains unexplained. “By the 2015-2017 period, 30-day death had returned to baseline levels,” he said.

In contrast, the HRRP, which was rolled out in 2012, has also been shown to reduce readmissions but, in most studies, 30-day mortality had gone up.

“The VA has a very robust quality infrastructure and a robust mechanism for prioritizing certain quality-improvement goals and getting them accomplished that I think they are underrecognized for,” said Leora Horwitz, MD, MHS, the director of the Center for Healthcare Innovation and Delivery Science at NYU Langone Medical Center, New York.

In an interview, she also noted some concern with the uptick seen in the 2011-2012 period, noting that the increase might be the same signal seen with the HRRP intervention.

“This is around the same time period where other people were writing the HRRP papers that showed an increase in mortality, so that’s something to consider,” she said.

Dr. Horwitz coauthored a study published in 2017 indicating that, on a hospital level (compared with a patient level, the approach most other studies took), reductions in readmissions were only weakly correlated with 30-day mortality rates after discharge.

“So, if you think that a hospital that’s behaving badly and keeping people out of the hospital inappropriately to cut down their readmissions, you’d expect to see increased mortality in that hospital, and in our study there was no correlation whatsoever. So there is still debate as to what is behind the increase in mortality on a patient level with heart failure that we’ve seen in some studies,” she said.

Dr. Horwitz doubts an intervention such as the one undertaken in the VA system – even with its fairly soft-touch “name and shame” component – would work in the non-VA hospital world.

“Those who have been in favor of financial penalties have pointed to the fact that, in general, it’s hard to get health systems to respond without financial alignment, even if it’s not an overt financial incentive,” she said.

“The VA is a unique environment,” she noted. “They have a very strong top-down command control focus where people are kind of used to being told, ‘OK, here are the measures we have to address this year.’ It’s good to see that the system that has worked for them for other outcomes also worked for them for heart failure readmissions too.”

Dr. Parizo has disclosed no relevant financial relationships. Dr. Horwitz has worked under contract to Medicare to develop readmission measures. 

A version of this article originally 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.

The number of suspicious lesions needed to refer to diagnose melanoma was 31.5, while the number needed to biopsy was 7.5. At the same time, the number needed to refer to diagnose non-melanoma skin cancer was 4 and the number needed to biopsy was 1.5.

The findings come from a retrospective review of 707 patients referred to a tertiary medical center dermatology practice for suspicious lesions, presented in a poster session at the virtual annual meeting of the American Academy of Dermatology

“Multiple studies in the dermatology literature have looked at the number needed to treat (NNT) as a quality metric for dermatology clinics, where a lower number is ‘better,’” the study’s first author, Nikolai Klebanov, MD, said in an interview following the virtual meeting. “Our particular study is unique in that we estimated both the number needed to refer and number needed to biopsy to closely examine the process of referrals for suspicious lesions from primary care settings to specialists. We also looked closely at the underlying patient-centered characteristics, which could be used by all clinicians to streamline the referral process by reducing the volume of low-risk referrals.”

Dr. Klebanov, of the department of dermatology at Massachusetts General Hospital, Boston, and his associates reviewed 707 unique patient visits to the department during July 2015–February 2016. They calculated the number needed to refer and biopsy for melanoma as the ratio of biopsy-proven melanoma diagnoses among benign and dysplastic nevi and seborrheic keratoses. For nonmelanoma skin cancer, they used the ratio of basal and squamous cell carcinoma among actinic keratoses and seborrheic keratoses.

Of the 707 patients, 54% were female, and males were slightly older than females (a mean of 58 vs. 54 years, respectively). The researchers found that lesions were more commonly benign among all age groups, while the frequency of premalignant and malignant lesions such as actinic keratoses, nonmelanoma skin cancer, and melanoma was highest for males and increased with age. Nevi were the most common benign diagnosis among patients 39 years of age and younger, while seborrheic keratoses were more common among patients aged 40 years and older.

The researchers found that the number needed to treat for melanoma was 31.5 and the number needed to biopsy was 7.5, which represents a 4.2-fold difference. Meanwhile, the number needed to refer for nonmelanoma skin cancer was 4, and the number needed to biopsy was 1.5, which represents a 2.7-fold difference. Despite variable rates of skin cancer between demographics, the biopsy rate ranged between 18% and 30%, for a mean of 23.4%.

“We found that most young patients referred for a ‘suspicious lesion’ on clinical prebiopsy assessment by the dermatologist were determined to actually have a benign nevus, and that older patients were most likely to have a seborrheic keratosis as the underlying lesion,” Dr. Klebanov said. “Among the minority of patients in each demographic group who were selected for biopsy, those lesions which were found to be benign were also largely nevi and keratoses. Even by being mindful of just the patient’s age, primary care providers can follow patients clinically with a tailored differential diagnosis in mind before referral, and dermatologists can reduce the number of biopsies they perform on patients who are being referred.”

He added that he and his colleagues were surprised that despite very low rates of skin cancer in young patients, and thus different pretest probabilities of cancer, biopsy rates across demographics were consistently around 20%. “We also found a disproportionate number of female patients younger than age 40 who were referred for suspicious lesions, while in the older age groups, the ratio of males to females was approximately equal.”

Dr. Klebanov acknowledged certain limitations of the study, including its single-center, retrospective design, and that information was not collected on patients’ family history of skin cancer, Fitzpatrick skin type, nor the clinical course of the lesion while it was followed by the primary care office. “The nuanced differences in these factors may certainly play a role in decisions for individual patients,” he said.

The study’s principal investigator was Hensin Tsao MD, PhD, clinical director of the MGH Melanoma & Pigmented Lesion Center The work was supported by the Alpha Omega Alpha Carolyn Kuckein Research Fellowship. The researchers reported having no financial disclosures.

[email protected]

SOURCE: Klebanov N et al. AAD 20. Abstract 15881.

The number of suspicious lesions needed to refer to diagnose melanoma was 31.5, while the number needed to biopsy was 7.5. At the same time, the number needed to refer to diagnose non-melanoma skin cancer was 4 and the number needed to biopsy was 1.5.

The findings come from a retrospective review of 707 patients referred to a tertiary medical center dermatology practice for suspicious lesions, presented in a poster session at the virtual annual meeting of the American Academy of Dermatology

“Multiple studies in the dermatology literature have looked at the number needed to treat (NNT) as a quality metric for dermatology clinics, where a lower number is ‘better,’” the study’s first author, Nikolai Klebanov, MD, said in an interview following the virtual meeting. “Our particular study is unique in that we estimated both the number needed to refer and number needed to biopsy to closely examine the process of referrals for suspicious lesions from primary care settings to specialists. We also looked closely at the underlying patient-centered characteristics, which could be used by all clinicians to streamline the referral process by reducing the volume of low-risk referrals.”

Dr. Klebanov, of the department of dermatology at Massachusetts General Hospital, Boston, and his associates reviewed 707 unique patient visits to the department during July 2015–February 2016. They calculated the number needed to refer and biopsy for melanoma as the ratio of biopsy-proven melanoma diagnoses among benign and dysplastic nevi and seborrheic keratoses. For nonmelanoma skin cancer, they used the ratio of basal and squamous cell carcinoma among actinic keratoses and seborrheic keratoses.

Of the 707 patients, 54% were female, and males were slightly older than females (a mean of 58 vs. 54 years, respectively). The researchers found that lesions were more commonly benign among all age groups, while the frequency of premalignant and malignant lesions such as actinic keratoses, nonmelanoma skin cancer, and melanoma was highest for males and increased with age. Nevi were the most common benign diagnosis among patients 39 years of age and younger, while seborrheic keratoses were more common among patients aged 40 years and older.

The researchers found that the number needed to treat for melanoma was 31.5 and the number needed to biopsy was 7.5, which represents a 4.2-fold difference. Meanwhile, the number needed to refer for nonmelanoma skin cancer was 4, and the number needed to biopsy was 1.5, which represents a 2.7-fold difference. Despite variable rates of skin cancer between demographics, the biopsy rate ranged between 18% and 30%, for a mean of 23.4%.

“We found that most young patients referred for a ‘suspicious lesion’ on clinical prebiopsy assessment by the dermatologist were determined to actually have a benign nevus, and that older patients were most likely to have a seborrheic keratosis as the underlying lesion,” Dr. Klebanov said. “Among the minority of patients in each demographic group who were selected for biopsy, those lesions which were found to be benign were also largely nevi and keratoses. Even by being mindful of just the patient’s age, primary care providers can follow patients clinically with a tailored differential diagnosis in mind before referral, and dermatologists can reduce the number of biopsies they perform on patients who are being referred.”

He added that he and his colleagues were surprised that despite very low rates of skin cancer in young patients, and thus different pretest probabilities of cancer, biopsy rates across demographics were consistently around 20%. “We also found a disproportionate number of female patients younger than age 40 who were referred for suspicious lesions, while in the older age groups, the ratio of males to females was approximately equal.”

Dr. Klebanov acknowledged certain limitations of the study, including its single-center, retrospective design, and that information was not collected on patients’ family history of skin cancer, Fitzpatrick skin type, nor the clinical course of the lesion while it was followed by the primary care office. “The nuanced differences in these factors may certainly play a role in decisions for individual patients,” he said.

The study’s principal investigator was Hensin Tsao MD, PhD, clinical director of the MGH Melanoma & Pigmented Lesion Center The work was supported by the Alpha Omega Alpha Carolyn Kuckein Research Fellowship. The researchers reported having no financial disclosures.

[email protected]

SOURCE: Klebanov N et al. AAD 20. Abstract 15881.

The number of suspicious lesions needed to refer to diagnose melanoma was 31.5, while the number needed to biopsy was 7.5. At the same time, the number needed to refer to diagnose non-melanoma skin cancer was 4 and the number needed to biopsy was 1.5.

The findings come from a retrospective review of 707 patients referred to a tertiary medical center dermatology practice for suspicious lesions, presented in a poster session at the virtual annual meeting of the American Academy of Dermatology

“Multiple studies in the dermatology literature have looked at the number needed to treat (NNT) as a quality metric for dermatology clinics, where a lower number is ‘better,’” the study’s first author, Nikolai Klebanov, MD, said in an interview following the virtual meeting. “Our particular study is unique in that we estimated both the number needed to refer and number needed to biopsy to closely examine the process of referrals for suspicious lesions from primary care settings to specialists. We also looked closely at the underlying patient-centered characteristics, which could be used by all clinicians to streamline the referral process by reducing the volume of low-risk referrals.”

Dr. Klebanov, of the department of dermatology at Massachusetts General Hospital, Boston, and his associates reviewed 707 unique patient visits to the department during July 2015–February 2016. They calculated the number needed to refer and biopsy for melanoma as the ratio of biopsy-proven melanoma diagnoses among benign and dysplastic nevi and seborrheic keratoses. For nonmelanoma skin cancer, they used the ratio of basal and squamous cell carcinoma among actinic keratoses and seborrheic keratoses.

Of the 707 patients, 54% were female, and males were slightly older than females (a mean of 58 vs. 54 years, respectively). The researchers found that lesions were more commonly benign among all age groups, while the frequency of premalignant and malignant lesions such as actinic keratoses, nonmelanoma skin cancer, and melanoma was highest for males and increased with age. Nevi were the most common benign diagnosis among patients 39 years of age and younger, while seborrheic keratoses were more common among patients aged 40 years and older.

The researchers found that the number needed to treat for melanoma was 31.5 and the number needed to biopsy was 7.5, which represents a 4.2-fold difference. Meanwhile, the number needed to refer for nonmelanoma skin cancer was 4, and the number needed to biopsy was 1.5, which represents a 2.7-fold difference. Despite variable rates of skin cancer between demographics, the biopsy rate ranged between 18% and 30%, for a mean of 23.4%.

“We found that most young patients referred for a ‘suspicious lesion’ on clinical prebiopsy assessment by the dermatologist were determined to actually have a benign nevus, and that older patients were most likely to have a seborrheic keratosis as the underlying lesion,” Dr. Klebanov said. “Among the minority of patients in each demographic group who were selected for biopsy, those lesions which were found to be benign were also largely nevi and keratoses. Even by being mindful of just the patient’s age, primary care providers can follow patients clinically with a tailored differential diagnosis in mind before referral, and dermatologists can reduce the number of biopsies they perform on patients who are being referred.”

He added that he and his colleagues were surprised that despite very low rates of skin cancer in young patients, and thus different pretest probabilities of cancer, biopsy rates across demographics were consistently around 20%. “We also found a disproportionate number of female patients younger than age 40 who were referred for suspicious lesions, while in the older age groups, the ratio of males to females was approximately equal.”

Dr. Klebanov acknowledged certain limitations of the study, including its single-center, retrospective design, and that information was not collected on patients’ family history of skin cancer, Fitzpatrick skin type, nor the clinical course of the lesion while it was followed by the primary care office. “The nuanced differences in these factors may certainly play a role in decisions for individual patients,” he said.

The study’s principal investigator was Hensin Tsao MD, PhD, clinical director of the MGH Melanoma & Pigmented Lesion Center The work was supported by the Alpha Omega Alpha Carolyn Kuckein Research Fellowship. The researchers reported having no financial disclosures.

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SOURCE: Klebanov N et al. AAD 20. Abstract 15881.