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Immune checkpoint inhibitors don’t increase COVID-19 incidence or mortality, studies suggest
Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.
However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.
In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).
In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).
Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
COVID-19 incidence with ICIs
Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.
The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).
In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).
Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.
“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”
COVID-19 mortality with ICIs
For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.
Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.
In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.
Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).
At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.
The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.
“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.
“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
ICI therapy can continue, with precautions
“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.
“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.
However, the findings of the study by Tyan and colleagues are more “thought-provoking,” Dr. Doroshow said. She noted that a large study published in Nature Medicine showed previous ICI therapy in cancer patients with COVID-19 increased the risk for hospitalization or severe COVID-19 requiring high-flow oxygen or mechanical ventilation. The new study was much smaller and did not perform statistical comparisons for outcomes such as oxygen requirements.
“I would feel comfortable telling patients that the data suggests that ICI treatment does not increase their risk of COVID-19. However, if they were to be diagnosed with COVID-19, it is unclear whether their previous ICI treatment increases their risk for poor outcomes,” Dr. Doroshow said.
“I would feel comfortable continuing to treat patients with ICIs at this time, but because we know that patients with cancer are generally more likely to develop COVID-19 and have poor outcomes, it is critical that our patients be educated about social distancing and mask wearing to the extent that their living and working situations permit,” she added.
Mr. Pahalyants disclosed no relevant conflicts of interest, and his study did not receive any specific funding. Mr. Tyan disclosed that he is cofounder and chief science officer of Kinnos, and his study did not receive any specific funding. Dr. Doroshow disclosed no relevant conflicts of interest.
SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.
Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.
However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.
In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).
In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).
Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
COVID-19 incidence with ICIs
Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.
The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).
In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).
Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.
“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”
COVID-19 mortality with ICIs
For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.
Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.
In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.
Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).
At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.
The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.
“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.
“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
ICI therapy can continue, with precautions
“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.
“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.
However, the findings of the study by Tyan and colleagues are more “thought-provoking,” Dr. Doroshow said. She noted that a large study published in Nature Medicine showed previous ICI therapy in cancer patients with COVID-19 increased the risk for hospitalization or severe COVID-19 requiring high-flow oxygen or mechanical ventilation. The new study was much smaller and did not perform statistical comparisons for outcomes such as oxygen requirements.
“I would feel comfortable telling patients that the data suggests that ICI treatment does not increase their risk of COVID-19. However, if they were to be diagnosed with COVID-19, it is unclear whether their previous ICI treatment increases their risk for poor outcomes,” Dr. Doroshow said.
“I would feel comfortable continuing to treat patients with ICIs at this time, but because we know that patients with cancer are generally more likely to develop COVID-19 and have poor outcomes, it is critical that our patients be educated about social distancing and mask wearing to the extent that their living and working situations permit,” she added.
Mr. Pahalyants disclosed no relevant conflicts of interest, and his study did not receive any specific funding. Mr. Tyan disclosed that he is cofounder and chief science officer of Kinnos, and his study did not receive any specific funding. Dr. Doroshow disclosed no relevant conflicts of interest.
SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.
Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.
However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.
In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).
In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).
Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
COVID-19 incidence with ICIs
Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.
The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).
In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).
Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.
“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”
COVID-19 mortality with ICIs
For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.
Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.
In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.
Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).
At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.
The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.
“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.
“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
ICI therapy can continue, with precautions
“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.
“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.
However, the findings of the study by Tyan and colleagues are more “thought-provoking,” Dr. Doroshow said. She noted that a large study published in Nature Medicine showed previous ICI therapy in cancer patients with COVID-19 increased the risk for hospitalization or severe COVID-19 requiring high-flow oxygen or mechanical ventilation. The new study was much smaller and did not perform statistical comparisons for outcomes such as oxygen requirements.
“I would feel comfortable telling patients that the data suggests that ICI treatment does not increase their risk of COVID-19. However, if they were to be diagnosed with COVID-19, it is unclear whether their previous ICI treatment increases their risk for poor outcomes,” Dr. Doroshow said.
“I would feel comfortable continuing to treat patients with ICIs at this time, but because we know that patients with cancer are generally more likely to develop COVID-19 and have poor outcomes, it is critical that our patients be educated about social distancing and mask wearing to the extent that their living and working situations permit,” she added.
Mr. Pahalyants disclosed no relevant conflicts of interest, and his study did not receive any specific funding. Mr. Tyan disclosed that he is cofounder and chief science officer of Kinnos, and his study did not receive any specific funding. Dr. Doroshow disclosed no relevant conflicts of interest.
SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.
FROM SITC 2020
Risk factors for severe immune-related AEs identified
The first nationwide study of severe immune-related adverse events among cancer patients treated with immune checkpoint inhibitors helps identify those at elevated risk. The findings were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.
“Immune-related adverse events are a very serious side effect of immune checkpoint inhibitor therapy, and as this therapy has become more common for treating advanced cancers, the incidence of immune-related adverse events has increased as well,” said presenting author William Murphy, a dual MD and MBA student at Harvard Medical School and Harvard Business School, both in Boston.
“However, because there is no ICD code for immune-related adverse events, it’s very difficult to study them at a population level. Most of the current literature around the incidence of immune-related adverse events and factors that are predictive of incidence are based on clinical trials and small studies,” Mr. Murphy noted.
He and his colleagues analyzed claims data from a U.S. nationwide health insurance plan for 14,378 patients who had a primary cancer and received at least one administration of an immune checkpoint inhibitor – an inhibitor of PD-1, PD-L1, or CTLA4 – during 2011-2019.
Over 19,117 patient-years of follow-up, 504 patients (3.5%) developed a severe immune-related adverse event (irAE), defined as one occurring within 2 years of their treatment and requiring inpatient hospitalization and new immunosuppression.
The incidence of severe irAEs per patient treatment year was 2.6% overall, rising from 0% in 2011 to 3.7% in 2016.
In multivariate analysis, patients had an elevated risk of severe irAEs if they received combination immunotherapy as compared with monotherapy (odds ratio, 2.44; P < .001).
On the other hand, risk fell with advancing age (OR, 0.98 per additional year; P < .001). And risk was lower for patients with melanoma (OR, 0.70; P = .01), renal cell carcinoma (OR, 0.71; P = .03), and other cancers (OR, 0.50; P < .001), compared with lung cancer.
Sex, geographic region, income, employment status, and comorbidity were not significantly associated with the risk of severe irAEs.
“We hope that patients and providers can use this evidence from a nationwide study of severe irAEs to guide treatment and management decisions,” Mr. Murphy concluded.
Real-world evidence
“As the use of immune checkpoint inhibitors increases for patients with a variety of different tumor types, there is increasing need for population-level evidence for patients treated outside of clinical trials,” said Allison Betof Warner, MD, PhD, an assistant attending physician with the melanoma service at Memorial Sloan Kettering Cancer Center in New York.
“This is a well-conducted study with an innovative approach to using real-world evidence to examine immune-related adverse events,” she added.
To her knowledge, it is the first study to look at multiple cancers for which immunotherapy is approved, Dr. Betof Warner said. This approach resulted in a large patient sample, giving power to detect differences between groups.
“The authors’ finding that combination immunotherapy is associated with more severe irAEs is in line with our clinical experience and other data sets, and the data regarding increased odds of severe irAEs in younger patients and those with lung cancer raise interesting biological questions about the etiology of irAEs,” Dr. Betof Warner noted.
However, certain factors complicate interpretation of the study’s findings, she cautioned. One such factor is requiring hospitalization to define an irAE.
“Practice patterns regarding hospitalization vary quite widely from center to center. For example, in some centers, all patients with immune-mediated colitis are hospitalized, whereas in others, these patients are managed predominantly in the outpatient setting, even in cases of high-grade toxicity,” she explained. “Practice patterns have also changed drastically over time as oncologists have grown more comfortable managing immune-related adverse events.”
Another factor is potential confounding. For example, patients with melanoma are more likely to receive combination immunotherapy given its longstanding approval for this cancer, whereas it is comparatively new for other cancers. Also, age may differ across cancers.
“The data the authors have provided are a great starting point, but I think further analysis is needed before these observations can be validated and integrated into practice,” Dr. Betof Warner concluded.
This study did not receive any specific funding. Mr. Murphy and Dr. Betof Warner disclosed no relevant conflicts of interest.
SOURCE: Murphy W et al. SITC 2020, Abstract 854.
The first nationwide study of severe immune-related adverse events among cancer patients treated with immune checkpoint inhibitors helps identify those at elevated risk. The findings were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.
“Immune-related adverse events are a very serious side effect of immune checkpoint inhibitor therapy, and as this therapy has become more common for treating advanced cancers, the incidence of immune-related adverse events has increased as well,” said presenting author William Murphy, a dual MD and MBA student at Harvard Medical School and Harvard Business School, both in Boston.
“However, because there is no ICD code for immune-related adverse events, it’s very difficult to study them at a population level. Most of the current literature around the incidence of immune-related adverse events and factors that are predictive of incidence are based on clinical trials and small studies,” Mr. Murphy noted.
He and his colleagues analyzed claims data from a U.S. nationwide health insurance plan for 14,378 patients who had a primary cancer and received at least one administration of an immune checkpoint inhibitor – an inhibitor of PD-1, PD-L1, or CTLA4 – during 2011-2019.
Over 19,117 patient-years of follow-up, 504 patients (3.5%) developed a severe immune-related adverse event (irAE), defined as one occurring within 2 years of their treatment and requiring inpatient hospitalization and new immunosuppression.
The incidence of severe irAEs per patient treatment year was 2.6% overall, rising from 0% in 2011 to 3.7% in 2016.
In multivariate analysis, patients had an elevated risk of severe irAEs if they received combination immunotherapy as compared with monotherapy (odds ratio, 2.44; P < .001).
On the other hand, risk fell with advancing age (OR, 0.98 per additional year; P < .001). And risk was lower for patients with melanoma (OR, 0.70; P = .01), renal cell carcinoma (OR, 0.71; P = .03), and other cancers (OR, 0.50; P < .001), compared with lung cancer.
Sex, geographic region, income, employment status, and comorbidity were not significantly associated with the risk of severe irAEs.
“We hope that patients and providers can use this evidence from a nationwide study of severe irAEs to guide treatment and management decisions,” Mr. Murphy concluded.
Real-world evidence
“As the use of immune checkpoint inhibitors increases for patients with a variety of different tumor types, there is increasing need for population-level evidence for patients treated outside of clinical trials,” said Allison Betof Warner, MD, PhD, an assistant attending physician with the melanoma service at Memorial Sloan Kettering Cancer Center in New York.
“This is a well-conducted study with an innovative approach to using real-world evidence to examine immune-related adverse events,” she added.
To her knowledge, it is the first study to look at multiple cancers for which immunotherapy is approved, Dr. Betof Warner said. This approach resulted in a large patient sample, giving power to detect differences between groups.
“The authors’ finding that combination immunotherapy is associated with more severe irAEs is in line with our clinical experience and other data sets, and the data regarding increased odds of severe irAEs in younger patients and those with lung cancer raise interesting biological questions about the etiology of irAEs,” Dr. Betof Warner noted.
However, certain factors complicate interpretation of the study’s findings, she cautioned. One such factor is requiring hospitalization to define an irAE.
“Practice patterns regarding hospitalization vary quite widely from center to center. For example, in some centers, all patients with immune-mediated colitis are hospitalized, whereas in others, these patients are managed predominantly in the outpatient setting, even in cases of high-grade toxicity,” she explained. “Practice patterns have also changed drastically over time as oncologists have grown more comfortable managing immune-related adverse events.”
Another factor is potential confounding. For example, patients with melanoma are more likely to receive combination immunotherapy given its longstanding approval for this cancer, whereas it is comparatively new for other cancers. Also, age may differ across cancers.
“The data the authors have provided are a great starting point, but I think further analysis is needed before these observations can be validated and integrated into practice,” Dr. Betof Warner concluded.
This study did not receive any specific funding. Mr. Murphy and Dr. Betof Warner disclosed no relevant conflicts of interest.
SOURCE: Murphy W et al. SITC 2020, Abstract 854.
The first nationwide study of severe immune-related adverse events among cancer patients treated with immune checkpoint inhibitors helps identify those at elevated risk. The findings were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.
“Immune-related adverse events are a very serious side effect of immune checkpoint inhibitor therapy, and as this therapy has become more common for treating advanced cancers, the incidence of immune-related adverse events has increased as well,” said presenting author William Murphy, a dual MD and MBA student at Harvard Medical School and Harvard Business School, both in Boston.
“However, because there is no ICD code for immune-related adverse events, it’s very difficult to study them at a population level. Most of the current literature around the incidence of immune-related adverse events and factors that are predictive of incidence are based on clinical trials and small studies,” Mr. Murphy noted.
He and his colleagues analyzed claims data from a U.S. nationwide health insurance plan for 14,378 patients who had a primary cancer and received at least one administration of an immune checkpoint inhibitor – an inhibitor of PD-1, PD-L1, or CTLA4 – during 2011-2019.
Over 19,117 patient-years of follow-up, 504 patients (3.5%) developed a severe immune-related adverse event (irAE), defined as one occurring within 2 years of their treatment and requiring inpatient hospitalization and new immunosuppression.
The incidence of severe irAEs per patient treatment year was 2.6% overall, rising from 0% in 2011 to 3.7% in 2016.
In multivariate analysis, patients had an elevated risk of severe irAEs if they received combination immunotherapy as compared with monotherapy (odds ratio, 2.44; P < .001).
On the other hand, risk fell with advancing age (OR, 0.98 per additional year; P < .001). And risk was lower for patients with melanoma (OR, 0.70; P = .01), renal cell carcinoma (OR, 0.71; P = .03), and other cancers (OR, 0.50; P < .001), compared with lung cancer.
Sex, geographic region, income, employment status, and comorbidity were not significantly associated with the risk of severe irAEs.
“We hope that patients and providers can use this evidence from a nationwide study of severe irAEs to guide treatment and management decisions,” Mr. Murphy concluded.
Real-world evidence
“As the use of immune checkpoint inhibitors increases for patients with a variety of different tumor types, there is increasing need for population-level evidence for patients treated outside of clinical trials,” said Allison Betof Warner, MD, PhD, an assistant attending physician with the melanoma service at Memorial Sloan Kettering Cancer Center in New York.
“This is a well-conducted study with an innovative approach to using real-world evidence to examine immune-related adverse events,” she added.
To her knowledge, it is the first study to look at multiple cancers for which immunotherapy is approved, Dr. Betof Warner said. This approach resulted in a large patient sample, giving power to detect differences between groups.
“The authors’ finding that combination immunotherapy is associated with more severe irAEs is in line with our clinical experience and other data sets, and the data regarding increased odds of severe irAEs in younger patients and those with lung cancer raise interesting biological questions about the etiology of irAEs,” Dr. Betof Warner noted.
However, certain factors complicate interpretation of the study’s findings, she cautioned. One such factor is requiring hospitalization to define an irAE.
“Practice patterns regarding hospitalization vary quite widely from center to center. For example, in some centers, all patients with immune-mediated colitis are hospitalized, whereas in others, these patients are managed predominantly in the outpatient setting, even in cases of high-grade toxicity,” she explained. “Practice patterns have also changed drastically over time as oncologists have grown more comfortable managing immune-related adverse events.”
Another factor is potential confounding. For example, patients with melanoma are more likely to receive combination immunotherapy given its longstanding approval for this cancer, whereas it is comparatively new for other cancers. Also, age may differ across cancers.
“The data the authors have provided are a great starting point, but I think further analysis is needed before these observations can be validated and integrated into practice,” Dr. Betof Warner concluded.
This study did not receive any specific funding. Mr. Murphy and Dr. Betof Warner disclosed no relevant conflicts of interest.
SOURCE: Murphy W et al. SITC 2020, Abstract 854.
FROM SITC 2020
Using telehealth to deliver palliative care to cancer patients
Traditional delivery of palliative care to outpatients with cancer is associated with many challenges.
Telehealth can eliminate some of these challenges but comes with issues of its own, according to results of the REACH PC trial.
Jennifer S. Temel, MD, of Massachusetts General Hospital in Boston, discussed the use of telemedicine in palliative care, including results from REACH PC, during an educational session at the ASCO Virtual Quality Care Symposium 2020.
Dr. Temel noted that, for cancer patients, an in-person visit with a palliative care specialist can cost time, induce fatigue, and increase financial burden from transportation and parking expenses.
For caregivers and family, an in-person visit may necessitate absence from family and/or work, require complex scheduling to coordinate with other office visits, and result in additional transportation and/or parking expenses.
For health care systems, to have a dedicated palliative care clinic requires precious space and financial expenditures for office personnel and other resources.
These issues make it attractive to consider whether telehealth could be used for palliative care services.
Scarcity of palliative care specialists
In the United States, there is roughly 1 palliative care physician for every 20,000 older adults with a life-limiting illness, according to research published in Annual Review of Public Health in 2014.
In its 2019 state-by-state report card, the Center to Advance Palliative Care noted that only 72% of U.S. hospitals with 50 or more beds have a palliative care team.
For patients with serious illnesses and those who are socioeconomically or geographically disadvantaged, palliative care is often inaccessible.
Inefficiencies in the current system are an additional impediment. Palliative care specialists frequently see patients during a portion of the patient’s routine visit to subspecialty or primary care clinics. This limits the palliative care specialist’s ability to perform comprehensive assessments and provide patient-centered care efficiently.
Special considerations regarding telehealth for palliative care
As a specialty, palliative care involves interactions that could make the use of telehealth problematic. For example, conveyance of interest, warmth, and touch are challenging or impossible in a video format.
Palliative care specialists engage with patients regarding relatively serious topics such as prognosis and end-of-life preferences. There is uncertainty about how those discussions would be received by patients and their caregivers via video.
Furthermore, there are logistical impediments such as prescribing opioids with video or across state lines.
Despite these concerns, the ENABLE study showed that supplementing usual oncology care with weekly (transitioning to monthly) telephone-based educational palliative care produced higher quality of life and mood than did usual oncology care alone. These results were published in JAMA in 2009.
REACH PC study demonstrates feasibility of telehealth model
Dr. Temel described the ongoing REACH PC trial in which palliative care is delivered via video visits and compared with in-person palliative care for patients with advanced non–small cell lung cancer.
The primary aim of REACH PC is to determine whether telehealth palliative care is equivalent to traditional palliative care in improving quality of life as a supplement to routine oncology care.
Currently, REACH PC has enrolled 581 patients at its 20 sites, spanning a geographically diverse area. Just over half of patients approached about REACH PC agreed to enroll in it. Ultimately, 1,250 enrollees are sought.
Among patients who declined to participate, 7.6% indicated “discomfort with technology” as the reason. Most refusals were due to lack of interest in research (35.1%) and/or palliative care (22.9%).
Older adults were prominent among enrollees. More than 60% were older than 60 years of age, and more than one-third were older than 70 years.
Among patients who began the trial, there were slightly more withdrawals in the telehealth participants, in comparison with in-person participants (13.6% versus 9.1%).
When palliative care clinicians were queried about video visits, 64.3% said there were no challenges. This is comparable to the 65.5% of clinicians who had no challenges with in-person visits.
When problems occurred with video visits, they were most frequently technical (19.1%). Only 1.4% of clinicians reported difficulty addressing topics that felt uncomfortable over video, and 1.5% reported difficulty establishing rapport.
The success rates of video and in-person visits were similar. About 80% of visits accomplished planned goals.
‘Webside’ manner
Strategies such as reflective listening and summarizing what patients say (to verify an accurate understanding of the patient’s perspective) are key to successful palliative care visits, regardless of the setting.
For telehealth visits, Dr. Temel described techniques she defined as “webside manner,” to compensate for the inability of the clinician to touch a patient. These techniques include leaning in toward the camera, nodding, and pausing to be certain the patient has finished speaking before the clinician speaks again.
Is telehealth the future of palliative care?
I include myself among those oncologists who have voiced concern about moving from face-to-face to remote visits for complicated consultations such as those required for palliative care. Nonetheless, from the preliminary results of the REACH PC trial, it appears that telehealth could be a valuable tool.
To minimize differences between in-person and remote delivery of palliative care, practical strategies for ensuring rapport and facilitating a trusting relationship should be defined further and disseminated.
In addition, we need to be vigilant for widening inequities of care from rapid movement to the use of technology (i.e., an equity gap). In their telehealth experience during the COVID-19 pandemic, investigators at Houston Methodist Cancer Center found that patients declining virtual visits tended to be older, lower-income, and less likely to have commercial insurance. These results were recently published in JCO Oncology Practice.
For the foregoing reasons, hybrid systems for palliative care services will probably always be needed.
Going forward, we should heed the advice of Alvin Toffler in his book Future Shock. Mr. Toffler said, “The illiterate of the 21st century will not be those who cannot read and write, but those who cannot learn, unlearn, and relearn.”
The traditional model for delivering palliative care will almost certainly need to be reimagined and relearned.
Dr. Temel disclosed institutional research funding from Pfizer.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Traditional delivery of palliative care to outpatients with cancer is associated with many challenges.
Telehealth can eliminate some of these challenges but comes with issues of its own, according to results of the REACH PC trial.
Jennifer S. Temel, MD, of Massachusetts General Hospital in Boston, discussed the use of telemedicine in palliative care, including results from REACH PC, during an educational session at the ASCO Virtual Quality Care Symposium 2020.
Dr. Temel noted that, for cancer patients, an in-person visit with a palliative care specialist can cost time, induce fatigue, and increase financial burden from transportation and parking expenses.
For caregivers and family, an in-person visit may necessitate absence from family and/or work, require complex scheduling to coordinate with other office visits, and result in additional transportation and/or parking expenses.
For health care systems, to have a dedicated palliative care clinic requires precious space and financial expenditures for office personnel and other resources.
These issues make it attractive to consider whether telehealth could be used for palliative care services.
Scarcity of palliative care specialists
In the United States, there is roughly 1 palliative care physician for every 20,000 older adults with a life-limiting illness, according to research published in Annual Review of Public Health in 2014.
In its 2019 state-by-state report card, the Center to Advance Palliative Care noted that only 72% of U.S. hospitals with 50 or more beds have a palliative care team.
For patients with serious illnesses and those who are socioeconomically or geographically disadvantaged, palliative care is often inaccessible.
Inefficiencies in the current system are an additional impediment. Palliative care specialists frequently see patients during a portion of the patient’s routine visit to subspecialty or primary care clinics. This limits the palliative care specialist’s ability to perform comprehensive assessments and provide patient-centered care efficiently.
Special considerations regarding telehealth for palliative care
As a specialty, palliative care involves interactions that could make the use of telehealth problematic. For example, conveyance of interest, warmth, and touch are challenging or impossible in a video format.
Palliative care specialists engage with patients regarding relatively serious topics such as prognosis and end-of-life preferences. There is uncertainty about how those discussions would be received by patients and their caregivers via video.
Furthermore, there are logistical impediments such as prescribing opioids with video or across state lines.
Despite these concerns, the ENABLE study showed that supplementing usual oncology care with weekly (transitioning to monthly) telephone-based educational palliative care produced higher quality of life and mood than did usual oncology care alone. These results were published in JAMA in 2009.
REACH PC study demonstrates feasibility of telehealth model
Dr. Temel described the ongoing REACH PC trial in which palliative care is delivered via video visits and compared with in-person palliative care for patients with advanced non–small cell lung cancer.
The primary aim of REACH PC is to determine whether telehealth palliative care is equivalent to traditional palliative care in improving quality of life as a supplement to routine oncology care.
Currently, REACH PC has enrolled 581 patients at its 20 sites, spanning a geographically diverse area. Just over half of patients approached about REACH PC agreed to enroll in it. Ultimately, 1,250 enrollees are sought.
Among patients who declined to participate, 7.6% indicated “discomfort with technology” as the reason. Most refusals were due to lack of interest in research (35.1%) and/or palliative care (22.9%).
Older adults were prominent among enrollees. More than 60% were older than 60 years of age, and more than one-third were older than 70 years.
Among patients who began the trial, there were slightly more withdrawals in the telehealth participants, in comparison with in-person participants (13.6% versus 9.1%).
When palliative care clinicians were queried about video visits, 64.3% said there were no challenges. This is comparable to the 65.5% of clinicians who had no challenges with in-person visits.
When problems occurred with video visits, they were most frequently technical (19.1%). Only 1.4% of clinicians reported difficulty addressing topics that felt uncomfortable over video, and 1.5% reported difficulty establishing rapport.
The success rates of video and in-person visits were similar. About 80% of visits accomplished planned goals.
‘Webside’ manner
Strategies such as reflective listening and summarizing what patients say (to verify an accurate understanding of the patient’s perspective) are key to successful palliative care visits, regardless of the setting.
For telehealth visits, Dr. Temel described techniques she defined as “webside manner,” to compensate for the inability of the clinician to touch a patient. These techniques include leaning in toward the camera, nodding, and pausing to be certain the patient has finished speaking before the clinician speaks again.
Is telehealth the future of palliative care?
I include myself among those oncologists who have voiced concern about moving from face-to-face to remote visits for complicated consultations such as those required for palliative care. Nonetheless, from the preliminary results of the REACH PC trial, it appears that telehealth could be a valuable tool.
To minimize differences between in-person and remote delivery of palliative care, practical strategies for ensuring rapport and facilitating a trusting relationship should be defined further and disseminated.
In addition, we need to be vigilant for widening inequities of care from rapid movement to the use of technology (i.e., an equity gap). In their telehealth experience during the COVID-19 pandemic, investigators at Houston Methodist Cancer Center found that patients declining virtual visits tended to be older, lower-income, and less likely to have commercial insurance. These results were recently published in JCO Oncology Practice.
For the foregoing reasons, hybrid systems for palliative care services will probably always be needed.
Going forward, we should heed the advice of Alvin Toffler in his book Future Shock. Mr. Toffler said, “The illiterate of the 21st century will not be those who cannot read and write, but those who cannot learn, unlearn, and relearn.”
The traditional model for delivering palliative care will almost certainly need to be reimagined and relearned.
Dr. Temel disclosed institutional research funding from Pfizer.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Traditional delivery of palliative care to outpatients with cancer is associated with many challenges.
Telehealth can eliminate some of these challenges but comes with issues of its own, according to results of the REACH PC trial.
Jennifer S. Temel, MD, of Massachusetts General Hospital in Boston, discussed the use of telemedicine in palliative care, including results from REACH PC, during an educational session at the ASCO Virtual Quality Care Symposium 2020.
Dr. Temel noted that, for cancer patients, an in-person visit with a palliative care specialist can cost time, induce fatigue, and increase financial burden from transportation and parking expenses.
For caregivers and family, an in-person visit may necessitate absence from family and/or work, require complex scheduling to coordinate with other office visits, and result in additional transportation and/or parking expenses.
For health care systems, to have a dedicated palliative care clinic requires precious space and financial expenditures for office personnel and other resources.
These issues make it attractive to consider whether telehealth could be used for palliative care services.
Scarcity of palliative care specialists
In the United States, there is roughly 1 palliative care physician for every 20,000 older adults with a life-limiting illness, according to research published in Annual Review of Public Health in 2014.
In its 2019 state-by-state report card, the Center to Advance Palliative Care noted that only 72% of U.S. hospitals with 50 or more beds have a palliative care team.
For patients with serious illnesses and those who are socioeconomically or geographically disadvantaged, palliative care is often inaccessible.
Inefficiencies in the current system are an additional impediment. Palliative care specialists frequently see patients during a portion of the patient’s routine visit to subspecialty or primary care clinics. This limits the palliative care specialist’s ability to perform comprehensive assessments and provide patient-centered care efficiently.
Special considerations regarding telehealth for palliative care
As a specialty, palliative care involves interactions that could make the use of telehealth problematic. For example, conveyance of interest, warmth, and touch are challenging or impossible in a video format.
Palliative care specialists engage with patients regarding relatively serious topics such as prognosis and end-of-life preferences. There is uncertainty about how those discussions would be received by patients and their caregivers via video.
Furthermore, there are logistical impediments such as prescribing opioids with video or across state lines.
Despite these concerns, the ENABLE study showed that supplementing usual oncology care with weekly (transitioning to monthly) telephone-based educational palliative care produced higher quality of life and mood than did usual oncology care alone. These results were published in JAMA in 2009.
REACH PC study demonstrates feasibility of telehealth model
Dr. Temel described the ongoing REACH PC trial in which palliative care is delivered via video visits and compared with in-person palliative care for patients with advanced non–small cell lung cancer.
The primary aim of REACH PC is to determine whether telehealth palliative care is equivalent to traditional palliative care in improving quality of life as a supplement to routine oncology care.
Currently, REACH PC has enrolled 581 patients at its 20 sites, spanning a geographically diverse area. Just over half of patients approached about REACH PC agreed to enroll in it. Ultimately, 1,250 enrollees are sought.
Among patients who declined to participate, 7.6% indicated “discomfort with technology” as the reason. Most refusals were due to lack of interest in research (35.1%) and/or palliative care (22.9%).
Older adults were prominent among enrollees. More than 60% were older than 60 years of age, and more than one-third were older than 70 years.
Among patients who began the trial, there were slightly more withdrawals in the telehealth participants, in comparison with in-person participants (13.6% versus 9.1%).
When palliative care clinicians were queried about video visits, 64.3% said there were no challenges. This is comparable to the 65.5% of clinicians who had no challenges with in-person visits.
When problems occurred with video visits, they were most frequently technical (19.1%). Only 1.4% of clinicians reported difficulty addressing topics that felt uncomfortable over video, and 1.5% reported difficulty establishing rapport.
The success rates of video and in-person visits were similar. About 80% of visits accomplished planned goals.
‘Webside’ manner
Strategies such as reflective listening and summarizing what patients say (to verify an accurate understanding of the patient’s perspective) are key to successful palliative care visits, regardless of the setting.
For telehealth visits, Dr. Temel described techniques she defined as “webside manner,” to compensate for the inability of the clinician to touch a patient. These techniques include leaning in toward the camera, nodding, and pausing to be certain the patient has finished speaking before the clinician speaks again.
Is telehealth the future of palliative care?
I include myself among those oncologists who have voiced concern about moving from face-to-face to remote visits for complicated consultations such as those required for palliative care. Nonetheless, from the preliminary results of the REACH PC trial, it appears that telehealth could be a valuable tool.
To minimize differences between in-person and remote delivery of palliative care, practical strategies for ensuring rapport and facilitating a trusting relationship should be defined further and disseminated.
In addition, we need to be vigilant for widening inequities of care from rapid movement to the use of technology (i.e., an equity gap). In their telehealth experience during the COVID-19 pandemic, investigators at Houston Methodist Cancer Center found that patients declining virtual visits tended to be older, lower-income, and less likely to have commercial insurance. These results were recently published in JCO Oncology Practice.
For the foregoing reasons, hybrid systems for palliative care services will probably always be needed.
Going forward, we should heed the advice of Alvin Toffler in his book Future Shock. Mr. Toffler said, “The illiterate of the 21st century will not be those who cannot read and write, but those who cannot learn, unlearn, and relearn.”
The traditional model for delivering palliative care will almost certainly need to be reimagined and relearned.
Dr. Temel disclosed institutional research funding from Pfizer.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
FROM ASCO QUALITY CARE SYMPOSIUM 2020
Predictors of upstaging on PSMA PET/CT may help guide its use
Routinely collected clinical data help identify men with high-risk prostate cancer most likely to benefit from a gallium-68 prostate-specific membrane antigen (PSMA) PET/CT scan, according to a study reported at the American Society for Radiation Oncology Annual Meeting 2020.
“PSMA PET/CT is a novel molecular and functional imaging modality specific for prostate cancer cells that has good sensitivity and outstanding specificity in detecting metastasis,” noted study investigator T. Martin Ma, MD, PhD, of the University of California, Los Angeles.
The proPSMA trial, published in The Lancet earlier this year, found PSMA PET/CT to be superior to conventional imaging for primary staging of high-risk prostate cancer.
“These findings carry significant clinical implications and can affect treatment decision-making,” Dr. Ma noted.
With the current study, Dr. Ma and colleagues set out to assess the impact of PSMA PET/CT in nodal and metastatic upstaging in patients with high-risk prostate cancer and explore predictors of upstaging.
The researchers conducted a post hoc analysis of a single-center, prospective study of 262 patients with high-risk prostate cancer (cN1 or cN0 on conventional imaging) undergoing primary staging. Patients who had received 3 or more months of androgen deprivation therapy before their scan were excluded.
Study results
PSMA PET/CT led to nodal upstaging – from N0 to N1 – in 19.7% of patients and metastasis upstaging – from M0 to M1a, b, or c – in 9.4%.
“It is worth pointing out that the percentage of upstaging at the PSMA scan in our study is very similar to that in the proPSMA study,” Dr. Ma noted, with that trial finding nodal upstaging in 18% of patients and metastasis upstaging in 8%.
In multivariate analysis, independent predictors of nodal upstaging with PSMA PET/CT were higher percentage of positive cores at biopsy (odds ratio per decile, 1.21; P = .001) and higher Gleason grade (OR, 1.61; P = .025).
Similarly, independent predictors of metastasis upstaging were higher percentage of positive cores at biopsy (OR per decile, 1.19; P = .013) and higher Gleason grade (OR, 2.13; P = .024).
Other factors – clinical T stage and N stage, initial prostate-specific antigen level, and presence of two or more high-risk features – did not independently predict these outcomes.
When various combinations were assessed, the incidence of nodal upstaging was highest for patients who had a Gleason grade of 4 or 5 plus at least 50% positive cores (27.5% vs. 13.1% among all others). Similarly, incidence of metastasis upstaging was highest for those who had a Gleason grade of 5 plus at least 50% positive cores (20.6% vs. 5.9% among all others).
“Patients with percent-positive cores of 50% or more and Gleason grade group 4 or 5 will benefit the most from a PSMA PET/CT scan,” Dr. Ma concluded. “Future studies should validate the importance of these factors and identify whether changing treatment leads to improved outcomes.”
“The beauty of percent-positive cores is that it is an objective and routinely available piece of clinical information from systematic biopsy,” he added. “It may aid in the selection of patients in resource-limited settings and consideration of treatment intensification. We may also consider incorporation of percent positive cores into clinical risk stratification schemes for clinical use.”
A game changer
“PSMA PET has been a real game changer in high-risk prostate cancer and has implications in the various stages of prostate cancer management from diagnosis and staging to theranostics,” said Renu Eapen, MBBS, of Peter MacCallum Cancer Centre in Melbourne, who was not involved in this study.
“PSMA PET/CT has challenged conventional imaging in staging before curative intent surgery or radiotherapy,” Dr. Eapen added.
Accuracy of PSMA PET/CT was 27% higher than that of conventional imaging in the proPSMA trial, she noted in an interview. This superior accuracy can ultimately have management impact, while the imaging has additional benefits of lower radiation dose and reproducibility with high reporter agreement, potentially making it a “one-stop-shop” scan.
“This prospective study by Ma et al. is a great adjunct to the proPSMA results, with the aims of further stratifying patients who are likely to be upstaged on PSMA PET/CT,” Dr. Eapen said. “As the availability of PSMA PET/CT increases and more centers adopt this technology, we need studies like these to risk-stratify patients and select those who would benefit.”
The study did not receive any specific funding. Dr. Ma and Dr. Eapen disclosed no conflicts of interest.
SOURCE: Ma TM et al. ASTRO 2020, Abstract 58.
Routinely collected clinical data help identify men with high-risk prostate cancer most likely to benefit from a gallium-68 prostate-specific membrane antigen (PSMA) PET/CT scan, according to a study reported at the American Society for Radiation Oncology Annual Meeting 2020.
“PSMA PET/CT is a novel molecular and functional imaging modality specific for prostate cancer cells that has good sensitivity and outstanding specificity in detecting metastasis,” noted study investigator T. Martin Ma, MD, PhD, of the University of California, Los Angeles.
The proPSMA trial, published in The Lancet earlier this year, found PSMA PET/CT to be superior to conventional imaging for primary staging of high-risk prostate cancer.
“These findings carry significant clinical implications and can affect treatment decision-making,” Dr. Ma noted.
With the current study, Dr. Ma and colleagues set out to assess the impact of PSMA PET/CT in nodal and metastatic upstaging in patients with high-risk prostate cancer and explore predictors of upstaging.
The researchers conducted a post hoc analysis of a single-center, prospective study of 262 patients with high-risk prostate cancer (cN1 or cN0 on conventional imaging) undergoing primary staging. Patients who had received 3 or more months of androgen deprivation therapy before their scan were excluded.
Study results
PSMA PET/CT led to nodal upstaging – from N0 to N1 – in 19.7% of patients and metastasis upstaging – from M0 to M1a, b, or c – in 9.4%.
“It is worth pointing out that the percentage of upstaging at the PSMA scan in our study is very similar to that in the proPSMA study,” Dr. Ma noted, with that trial finding nodal upstaging in 18% of patients and metastasis upstaging in 8%.
In multivariate analysis, independent predictors of nodal upstaging with PSMA PET/CT were higher percentage of positive cores at biopsy (odds ratio per decile, 1.21; P = .001) and higher Gleason grade (OR, 1.61; P = .025).
Similarly, independent predictors of metastasis upstaging were higher percentage of positive cores at biopsy (OR per decile, 1.19; P = .013) and higher Gleason grade (OR, 2.13; P = .024).
Other factors – clinical T stage and N stage, initial prostate-specific antigen level, and presence of two or more high-risk features – did not independently predict these outcomes.
When various combinations were assessed, the incidence of nodal upstaging was highest for patients who had a Gleason grade of 4 or 5 plus at least 50% positive cores (27.5% vs. 13.1% among all others). Similarly, incidence of metastasis upstaging was highest for those who had a Gleason grade of 5 plus at least 50% positive cores (20.6% vs. 5.9% among all others).
“Patients with percent-positive cores of 50% or more and Gleason grade group 4 or 5 will benefit the most from a PSMA PET/CT scan,” Dr. Ma concluded. “Future studies should validate the importance of these factors and identify whether changing treatment leads to improved outcomes.”
“The beauty of percent-positive cores is that it is an objective and routinely available piece of clinical information from systematic biopsy,” he added. “It may aid in the selection of patients in resource-limited settings and consideration of treatment intensification. We may also consider incorporation of percent positive cores into clinical risk stratification schemes for clinical use.”
A game changer
“PSMA PET has been a real game changer in high-risk prostate cancer and has implications in the various stages of prostate cancer management from diagnosis and staging to theranostics,” said Renu Eapen, MBBS, of Peter MacCallum Cancer Centre in Melbourne, who was not involved in this study.
“PSMA PET/CT has challenged conventional imaging in staging before curative intent surgery or radiotherapy,” Dr. Eapen added.
Accuracy of PSMA PET/CT was 27% higher than that of conventional imaging in the proPSMA trial, she noted in an interview. This superior accuracy can ultimately have management impact, while the imaging has additional benefits of lower radiation dose and reproducibility with high reporter agreement, potentially making it a “one-stop-shop” scan.
“This prospective study by Ma et al. is a great adjunct to the proPSMA results, with the aims of further stratifying patients who are likely to be upstaged on PSMA PET/CT,” Dr. Eapen said. “As the availability of PSMA PET/CT increases and more centers adopt this technology, we need studies like these to risk-stratify patients and select those who would benefit.”
The study did not receive any specific funding. Dr. Ma and Dr. Eapen disclosed no conflicts of interest.
SOURCE: Ma TM et al. ASTRO 2020, Abstract 58.
Routinely collected clinical data help identify men with high-risk prostate cancer most likely to benefit from a gallium-68 prostate-specific membrane antigen (PSMA) PET/CT scan, according to a study reported at the American Society for Radiation Oncology Annual Meeting 2020.
“PSMA PET/CT is a novel molecular and functional imaging modality specific for prostate cancer cells that has good sensitivity and outstanding specificity in detecting metastasis,” noted study investigator T. Martin Ma, MD, PhD, of the University of California, Los Angeles.
The proPSMA trial, published in The Lancet earlier this year, found PSMA PET/CT to be superior to conventional imaging for primary staging of high-risk prostate cancer.
“These findings carry significant clinical implications and can affect treatment decision-making,” Dr. Ma noted.
With the current study, Dr. Ma and colleagues set out to assess the impact of PSMA PET/CT in nodal and metastatic upstaging in patients with high-risk prostate cancer and explore predictors of upstaging.
The researchers conducted a post hoc analysis of a single-center, prospective study of 262 patients with high-risk prostate cancer (cN1 or cN0 on conventional imaging) undergoing primary staging. Patients who had received 3 or more months of androgen deprivation therapy before their scan were excluded.
Study results
PSMA PET/CT led to nodal upstaging – from N0 to N1 – in 19.7% of patients and metastasis upstaging – from M0 to M1a, b, or c – in 9.4%.
“It is worth pointing out that the percentage of upstaging at the PSMA scan in our study is very similar to that in the proPSMA study,” Dr. Ma noted, with that trial finding nodal upstaging in 18% of patients and metastasis upstaging in 8%.
In multivariate analysis, independent predictors of nodal upstaging with PSMA PET/CT were higher percentage of positive cores at biopsy (odds ratio per decile, 1.21; P = .001) and higher Gleason grade (OR, 1.61; P = .025).
Similarly, independent predictors of metastasis upstaging were higher percentage of positive cores at biopsy (OR per decile, 1.19; P = .013) and higher Gleason grade (OR, 2.13; P = .024).
Other factors – clinical T stage and N stage, initial prostate-specific antigen level, and presence of two or more high-risk features – did not independently predict these outcomes.
When various combinations were assessed, the incidence of nodal upstaging was highest for patients who had a Gleason grade of 4 or 5 plus at least 50% positive cores (27.5% vs. 13.1% among all others). Similarly, incidence of metastasis upstaging was highest for those who had a Gleason grade of 5 plus at least 50% positive cores (20.6% vs. 5.9% among all others).
“Patients with percent-positive cores of 50% or more and Gleason grade group 4 or 5 will benefit the most from a PSMA PET/CT scan,” Dr. Ma concluded. “Future studies should validate the importance of these factors and identify whether changing treatment leads to improved outcomes.”
“The beauty of percent-positive cores is that it is an objective and routinely available piece of clinical information from systematic biopsy,” he added. “It may aid in the selection of patients in resource-limited settings and consideration of treatment intensification. We may also consider incorporation of percent positive cores into clinical risk stratification schemes for clinical use.”
A game changer
“PSMA PET has been a real game changer in high-risk prostate cancer and has implications in the various stages of prostate cancer management from diagnosis and staging to theranostics,” said Renu Eapen, MBBS, of Peter MacCallum Cancer Centre in Melbourne, who was not involved in this study.
“PSMA PET/CT has challenged conventional imaging in staging before curative intent surgery or radiotherapy,” Dr. Eapen added.
Accuracy of PSMA PET/CT was 27% higher than that of conventional imaging in the proPSMA trial, she noted in an interview. This superior accuracy can ultimately have management impact, while the imaging has additional benefits of lower radiation dose and reproducibility with high reporter agreement, potentially making it a “one-stop-shop” scan.
“This prospective study by Ma et al. is a great adjunct to the proPSMA results, with the aims of further stratifying patients who are likely to be upstaged on PSMA PET/CT,” Dr. Eapen said. “As the availability of PSMA PET/CT increases and more centers adopt this technology, we need studies like these to risk-stratify patients and select those who would benefit.”
The study did not receive any specific funding. Dr. Ma and Dr. Eapen disclosed no conflicts of interest.
SOURCE: Ma TM et al. ASTRO 2020, Abstract 58.
FROM ASTRO 2020
Testicular cancer link to below-the-waist scans, x-rays?
Over the last 40 years, there has been a doubling in the incidence of testicular cancer. Over the same period, there has been a 20-fold increase in the use of diagnostic radiation, and the doses of radiation used have increased sevenfold. Perhaps the two are related?
The suggestion comes from researchers reporting a new case-control study in which they show that repeated diagnostic radiation below the waist was associated with an increase in the risk of testicular germ cell tumor (TGCT).
The study involved 315 men with TGCT and 931 controls from hospital and population-based settings. Researchers analyzed medical records and individuals’ recall of diagnostic radiation, such as CT scans, x-rays, and barium enema.
Compared with men who did not undergo any diagnostic radiation, the risk of testicular cancer was nearly twofold higher among men who had undergone three or more diagnostic x-rays and CT scans, and more than fourfold higher among men who had undergone three or more lower gastrointestinal series or barium enema.
The study was published online Nov. 11 in PLoS ONE.
Testicular cancer, the most common cancer in white men aged 15-44 years, has steadily increased in incidence in the United States over the past 3 or 4 decades. The rate has jumped from 3 out of 100,000 men in 1975 to 6 out of 100,000 men today, said senior author Katherine Nathanson, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
“Our data suggests that the increased use of diagnostic radiation below the waist in men over that same time may contribute to the increase in incidence,” Dr. Nathanson said in a press statement.
Reducing diagnostic radiation doses to the testes “should be prioritized,” said the investigators, if these results are validated by additional research.
It’s “undoubtedly prudent” to reduce those doses “as much as possible,” said David Brenner, PhD, director of the Center for Radiological Research, Columbia University Medical Center, New York.
However, Dr. Brenner also had reservations about the new study. “I do find the results quite surprising,” given what is known historically about testicular cancer and radiation exposure.
Higher radiation doses (than in the current study) in two other settings (among post–atomic bomb survivors and in the treatment of ankylosing spondylitis) are not associated with an increased risk of testicular cancer, Dr. Brenner said in an interview.
“Underlying conditions for which the individual received radiation imaging,” may be one potential explanation for the increased testicular cancer risk seen in this study, he added.
Dr. Nathanson responded to Dr. Brenner’s critique by focusing on atomic bomb survivors and pointing out that the baseline rate of testicular cancer in Asia, including Japan, is “very, very low” and therefore that population, including bomb survivors, is not a highly applicable comparison.
Take-home message: Testicular shielding
Dr. Nathanson noted that diagnostic imaging below the waist is most commonly administered as a result of GI tract complaints such as constipation and abdominal pain. For clinicians, the study’s take-home message supports testicular shielding.
Testicular shielding during diagnostic imaging can be protective, but audits show that correct use and positioning occurs in just 25% of pediatric diagnostic scans, the authors commented.
Recent epidemiologic studies support a tie between diagnostic radiation and other cancers, the authors also pointed out.
For example, women undergoing frequent x-rays for scoliosis may have an increased risk of breast cancer, and likewise for individuals undergoing repeat routine dental x-rays and thyroid cancer. Additionally, a National Health Service study among 175,000 children revealed an excess risk of subsequent brain tumors and leukemia tied to CT scans, said Dr. Nathanson and coauthors.
Total dose and number of exposures were associated with an increasing cancer risk in each of the aforementioned studies.
Dr. Nathanson pointed out that Penn researchers have collected testicular cancer data since 2001 for the sake of research on related, inherited risk. The new study is an outgrowth of those efforts and is a rare effort in this subject area, in part, because testicular cancer is a very treatable rare cancer, with a 95% survival rate at 5 years.
A larger prospective study of the association between diagnostic radiation and testicular cancer would be better for determining causality, but is impractical given the needed time and associated costs. “A case-control design is a methodology that is ideally suited for studies investigating rare disease outcomes such as TGCT,” the authors comment.
The study was supported with grants from the National Cancer Institute and the National Institutes of Health. The study authors and Dr. Brenner disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Over the last 40 years, there has been a doubling in the incidence of testicular cancer. Over the same period, there has been a 20-fold increase in the use of diagnostic radiation, and the doses of radiation used have increased sevenfold. Perhaps the two are related?
The suggestion comes from researchers reporting a new case-control study in which they show that repeated diagnostic radiation below the waist was associated with an increase in the risk of testicular germ cell tumor (TGCT).
The study involved 315 men with TGCT and 931 controls from hospital and population-based settings. Researchers analyzed medical records and individuals’ recall of diagnostic radiation, such as CT scans, x-rays, and barium enema.
Compared with men who did not undergo any diagnostic radiation, the risk of testicular cancer was nearly twofold higher among men who had undergone three or more diagnostic x-rays and CT scans, and more than fourfold higher among men who had undergone three or more lower gastrointestinal series or barium enema.
The study was published online Nov. 11 in PLoS ONE.
Testicular cancer, the most common cancer in white men aged 15-44 years, has steadily increased in incidence in the United States over the past 3 or 4 decades. The rate has jumped from 3 out of 100,000 men in 1975 to 6 out of 100,000 men today, said senior author Katherine Nathanson, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
“Our data suggests that the increased use of diagnostic radiation below the waist in men over that same time may contribute to the increase in incidence,” Dr. Nathanson said in a press statement.
Reducing diagnostic radiation doses to the testes “should be prioritized,” said the investigators, if these results are validated by additional research.
It’s “undoubtedly prudent” to reduce those doses “as much as possible,” said David Brenner, PhD, director of the Center for Radiological Research, Columbia University Medical Center, New York.
However, Dr. Brenner also had reservations about the new study. “I do find the results quite surprising,” given what is known historically about testicular cancer and radiation exposure.
Higher radiation doses (than in the current study) in two other settings (among post–atomic bomb survivors and in the treatment of ankylosing spondylitis) are not associated with an increased risk of testicular cancer, Dr. Brenner said in an interview.
“Underlying conditions for which the individual received radiation imaging,” may be one potential explanation for the increased testicular cancer risk seen in this study, he added.
Dr. Nathanson responded to Dr. Brenner’s critique by focusing on atomic bomb survivors and pointing out that the baseline rate of testicular cancer in Asia, including Japan, is “very, very low” and therefore that population, including bomb survivors, is not a highly applicable comparison.
Take-home message: Testicular shielding
Dr. Nathanson noted that diagnostic imaging below the waist is most commonly administered as a result of GI tract complaints such as constipation and abdominal pain. For clinicians, the study’s take-home message supports testicular shielding.
Testicular shielding during diagnostic imaging can be protective, but audits show that correct use and positioning occurs in just 25% of pediatric diagnostic scans, the authors commented.
Recent epidemiologic studies support a tie between diagnostic radiation and other cancers, the authors also pointed out.
For example, women undergoing frequent x-rays for scoliosis may have an increased risk of breast cancer, and likewise for individuals undergoing repeat routine dental x-rays and thyroid cancer. Additionally, a National Health Service study among 175,000 children revealed an excess risk of subsequent brain tumors and leukemia tied to CT scans, said Dr. Nathanson and coauthors.
Total dose and number of exposures were associated with an increasing cancer risk in each of the aforementioned studies.
Dr. Nathanson pointed out that Penn researchers have collected testicular cancer data since 2001 for the sake of research on related, inherited risk. The new study is an outgrowth of those efforts and is a rare effort in this subject area, in part, because testicular cancer is a very treatable rare cancer, with a 95% survival rate at 5 years.
A larger prospective study of the association between diagnostic radiation and testicular cancer would be better for determining causality, but is impractical given the needed time and associated costs. “A case-control design is a methodology that is ideally suited for studies investigating rare disease outcomes such as TGCT,” the authors comment.
The study was supported with grants from the National Cancer Institute and the National Institutes of Health. The study authors and Dr. Brenner disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Over the last 40 years, there has been a doubling in the incidence of testicular cancer. Over the same period, there has been a 20-fold increase in the use of diagnostic radiation, and the doses of radiation used have increased sevenfold. Perhaps the two are related?
The suggestion comes from researchers reporting a new case-control study in which they show that repeated diagnostic radiation below the waist was associated with an increase in the risk of testicular germ cell tumor (TGCT).
The study involved 315 men with TGCT and 931 controls from hospital and population-based settings. Researchers analyzed medical records and individuals’ recall of diagnostic radiation, such as CT scans, x-rays, and barium enema.
Compared with men who did not undergo any diagnostic radiation, the risk of testicular cancer was nearly twofold higher among men who had undergone three or more diagnostic x-rays and CT scans, and more than fourfold higher among men who had undergone three or more lower gastrointestinal series or barium enema.
The study was published online Nov. 11 in PLoS ONE.
Testicular cancer, the most common cancer in white men aged 15-44 years, has steadily increased in incidence in the United States over the past 3 or 4 decades. The rate has jumped from 3 out of 100,000 men in 1975 to 6 out of 100,000 men today, said senior author Katherine Nathanson, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
“Our data suggests that the increased use of diagnostic radiation below the waist in men over that same time may contribute to the increase in incidence,” Dr. Nathanson said in a press statement.
Reducing diagnostic radiation doses to the testes “should be prioritized,” said the investigators, if these results are validated by additional research.
It’s “undoubtedly prudent” to reduce those doses “as much as possible,” said David Brenner, PhD, director of the Center for Radiological Research, Columbia University Medical Center, New York.
However, Dr. Brenner also had reservations about the new study. “I do find the results quite surprising,” given what is known historically about testicular cancer and radiation exposure.
Higher radiation doses (than in the current study) in two other settings (among post–atomic bomb survivors and in the treatment of ankylosing spondylitis) are not associated with an increased risk of testicular cancer, Dr. Brenner said in an interview.
“Underlying conditions for which the individual received radiation imaging,” may be one potential explanation for the increased testicular cancer risk seen in this study, he added.
Dr. Nathanson responded to Dr. Brenner’s critique by focusing on atomic bomb survivors and pointing out that the baseline rate of testicular cancer in Asia, including Japan, is “very, very low” and therefore that population, including bomb survivors, is not a highly applicable comparison.
Take-home message: Testicular shielding
Dr. Nathanson noted that diagnostic imaging below the waist is most commonly administered as a result of GI tract complaints such as constipation and abdominal pain. For clinicians, the study’s take-home message supports testicular shielding.
Testicular shielding during diagnostic imaging can be protective, but audits show that correct use and positioning occurs in just 25% of pediatric diagnostic scans, the authors commented.
Recent epidemiologic studies support a tie between diagnostic radiation and other cancers, the authors also pointed out.
For example, women undergoing frequent x-rays for scoliosis may have an increased risk of breast cancer, and likewise for individuals undergoing repeat routine dental x-rays and thyroid cancer. Additionally, a National Health Service study among 175,000 children revealed an excess risk of subsequent brain tumors and leukemia tied to CT scans, said Dr. Nathanson and coauthors.
Total dose and number of exposures were associated with an increasing cancer risk in each of the aforementioned studies.
Dr. Nathanson pointed out that Penn researchers have collected testicular cancer data since 2001 for the sake of research on related, inherited risk. The new study is an outgrowth of those efforts and is a rare effort in this subject area, in part, because testicular cancer is a very treatable rare cancer, with a 95% survival rate at 5 years.
A larger prospective study of the association between diagnostic radiation and testicular cancer would be better for determining causality, but is impractical given the needed time and associated costs. “A case-control design is a methodology that is ideally suited for studies investigating rare disease outcomes such as TGCT,” the authors comment.
The study was supported with grants from the National Cancer Institute and the National Institutes of Health. The study authors and Dr. Brenner disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
New cancer drugs may have saved more than 1.2 million Americans
Reductions in mortality were most notable for tumor types with relatively more approvals, including lung and breast cancer, melanoma, lymphoma, and leukemia.
A report from the American Cancer Society (ACS) estimated that, from 1991 to 2017, there were 2,902,200 total cancer deaths avoided from improvements in mortality from all potential sources.
The new findings, reported in the Journal of Medical Economics, suggest that drugs approved between 2000 and 2016 to treat the 15 most common cancer types helped to reduce mortality by 24% per 100,000 people.
“This study provides evidence that a significant share of that reduction from 2000 to 2016 was associated with the introduction of new therapies. The ACS report and other studies demonstrate that the improvements in lung cancer specifically are likely due to new treatments,” said lead study author Joanna P. MacEwan, MD, of PRECISIONheor in Los Angeles.
The findings contribute to a better understanding of whether increased spending on cancer drugs are worth the investment, according to the study authors.
“We provide evidence that the gains in survival measured in clinical trials are translating into health benefits for patients in the real world and confirm previous research that has also shown that new pharmaceutical treatments are associated with improved real-world survival outcomes for patients,” Dr. MacEwan said.
Full effect not yet observed
The researchers used a series of national data sets from sources including the Centers for Disease Control and Prevention; the U.S. Mortality Files by the National Center of Health Statistics; Survival, Epidemiology and End Results program; and United States Cancer Statistics.
The team calculated age-adjusted cancer mortality rates per year for the 15 most common tumor types and also looked at incident cases of cancer by tumor type, represented as per 100,000 people, for all ages, races, and genders.
The researchers then translated the change in cancer mortality in the U.S. from 2000 to 2016 associated with treatment stocks in each year into deaths averted per year.
Across the 16 years, mortality was down by 1,291,769 deaths. The following cancers had significant reductions in mortality: breast (n = 127,874), colorectal (n = 46,705), lung (n = 375,256), prostate (n = 476,210), gastric (n = 758), and renal (n = 739) cancers, as well as non-Hodgkin lymphoma (n = 48,836) and leukemia (n = 4,011).
Estimated mortality increased by 825 deaths in patients with thyroid cancer and 7,768 deaths for those with bladder cancer. These rises are likely due to the result of sparse drug approvals during this period – five for thyroid cancer and three for bladder cancer – Dr. MacEwan said. There were no approvals in liver or uterine cancer and few approvals in pancreatic and oral cancer.
The full effect of new drug introductions may not have been observed yet, Dr. MacEwan noted.
“There are fewer patients using the treatments for drugs approved in the later years of our study and less follow-up time to measure outcomes,” she said. “Over time, utilization of the newer therapies will likely increase and the full effect on mortality will be observed.”
Other factors at play
Multiple factors have led to the declines in mortality, said William G. Cance, MD, chief medical and scientific officer for the ACS, who was not involved in this study. “We are slowly sorting out the explanations in greater granularity.”
Dr. MacEwan said improved cancer screening may partially explain the decline in mortality in some tumor types.
“If screening in a particular tumor type improved during the study period and tumors were diagnosed earlier, then mortality for that tumor type may decline,” she said. “However, we did not find strong evidence to suggest that there were significant changes in screening during our study period. Breast cancer screening rates, for example, were stable over our study period.”
Cancer screening is not as strong an influence as it should be, Dr. Cance said.
“The lung cancer screening rate is low. In breast and colorectal cancers, we need to double down on earlier screening,” he said, noting that less than one-quarter of adults between ages 45 and 50 years are currently screened for colorectal cancer. The ACS recommends that people at average risk of colorectal cancer start regular screening at age 45.
More research is necessary to evaluate the relationship between drug approvals and cancer mortality, Dr. MacEwan said.
“Research directly linking utilization of new therapies to improved survival or reduced mortality in the real-world setting would more definitively demonstrate the impact of new treatments,” she said. “New therapies have improved outcomes for many patients and should continue to be considered as key elements of cancer treatment.”
“We need to continue to reduce tobacco smoking and improve on modifiable behaviors at the same time as we work on getting new drugs to cancer patients,” Dr. Cance said. “We are coming into an era of multiple new therapeutics, including targeted therapies, immunotherapies, and cellular therapies. Clinicians need to look closely at the trial data of new drugs and pay close attention to those that have the most mortality impact.”
“We also need equitable distribution of newer drugs,” Dr. Cance added. “They should be distributed to everybody who deserves them. Mortality is often impacted by social determinants of health.”
Funding for this research was provided by Pfizer. Study authors disclosed relationships, including employment, with Pfizer. Dr. Cance had no disclosures.
SOURCE: MacEwan JP et al. J Med Econ. 2020 Nov 9;1-12.
Reductions in mortality were most notable for tumor types with relatively more approvals, including lung and breast cancer, melanoma, lymphoma, and leukemia.
A report from the American Cancer Society (ACS) estimated that, from 1991 to 2017, there were 2,902,200 total cancer deaths avoided from improvements in mortality from all potential sources.
The new findings, reported in the Journal of Medical Economics, suggest that drugs approved between 2000 and 2016 to treat the 15 most common cancer types helped to reduce mortality by 24% per 100,000 people.
“This study provides evidence that a significant share of that reduction from 2000 to 2016 was associated with the introduction of new therapies. The ACS report and other studies demonstrate that the improvements in lung cancer specifically are likely due to new treatments,” said lead study author Joanna P. MacEwan, MD, of PRECISIONheor in Los Angeles.
The findings contribute to a better understanding of whether increased spending on cancer drugs are worth the investment, according to the study authors.
“We provide evidence that the gains in survival measured in clinical trials are translating into health benefits for patients in the real world and confirm previous research that has also shown that new pharmaceutical treatments are associated with improved real-world survival outcomes for patients,” Dr. MacEwan said.
Full effect not yet observed
The researchers used a series of national data sets from sources including the Centers for Disease Control and Prevention; the U.S. Mortality Files by the National Center of Health Statistics; Survival, Epidemiology and End Results program; and United States Cancer Statistics.
The team calculated age-adjusted cancer mortality rates per year for the 15 most common tumor types and also looked at incident cases of cancer by tumor type, represented as per 100,000 people, for all ages, races, and genders.
The researchers then translated the change in cancer mortality in the U.S. from 2000 to 2016 associated with treatment stocks in each year into deaths averted per year.
Across the 16 years, mortality was down by 1,291,769 deaths. The following cancers had significant reductions in mortality: breast (n = 127,874), colorectal (n = 46,705), lung (n = 375,256), prostate (n = 476,210), gastric (n = 758), and renal (n = 739) cancers, as well as non-Hodgkin lymphoma (n = 48,836) and leukemia (n = 4,011).
Estimated mortality increased by 825 deaths in patients with thyroid cancer and 7,768 deaths for those with bladder cancer. These rises are likely due to the result of sparse drug approvals during this period – five for thyroid cancer and three for bladder cancer – Dr. MacEwan said. There were no approvals in liver or uterine cancer and few approvals in pancreatic and oral cancer.
The full effect of new drug introductions may not have been observed yet, Dr. MacEwan noted.
“There are fewer patients using the treatments for drugs approved in the later years of our study and less follow-up time to measure outcomes,” she said. “Over time, utilization of the newer therapies will likely increase and the full effect on mortality will be observed.”
Other factors at play
Multiple factors have led to the declines in mortality, said William G. Cance, MD, chief medical and scientific officer for the ACS, who was not involved in this study. “We are slowly sorting out the explanations in greater granularity.”
Dr. MacEwan said improved cancer screening may partially explain the decline in mortality in some tumor types.
“If screening in a particular tumor type improved during the study period and tumors were diagnosed earlier, then mortality for that tumor type may decline,” she said. “However, we did not find strong evidence to suggest that there were significant changes in screening during our study period. Breast cancer screening rates, for example, were stable over our study period.”
Cancer screening is not as strong an influence as it should be, Dr. Cance said.
“The lung cancer screening rate is low. In breast and colorectal cancers, we need to double down on earlier screening,” he said, noting that less than one-quarter of adults between ages 45 and 50 years are currently screened for colorectal cancer. The ACS recommends that people at average risk of colorectal cancer start regular screening at age 45.
More research is necessary to evaluate the relationship between drug approvals and cancer mortality, Dr. MacEwan said.
“Research directly linking utilization of new therapies to improved survival or reduced mortality in the real-world setting would more definitively demonstrate the impact of new treatments,” she said. “New therapies have improved outcomes for many patients and should continue to be considered as key elements of cancer treatment.”
“We need to continue to reduce tobacco smoking and improve on modifiable behaviors at the same time as we work on getting new drugs to cancer patients,” Dr. Cance said. “We are coming into an era of multiple new therapeutics, including targeted therapies, immunotherapies, and cellular therapies. Clinicians need to look closely at the trial data of new drugs and pay close attention to those that have the most mortality impact.”
“We also need equitable distribution of newer drugs,” Dr. Cance added. “They should be distributed to everybody who deserves them. Mortality is often impacted by social determinants of health.”
Funding for this research was provided by Pfizer. Study authors disclosed relationships, including employment, with Pfizer. Dr. Cance had no disclosures.
SOURCE: MacEwan JP et al. J Med Econ. 2020 Nov 9;1-12.
Reductions in mortality were most notable for tumor types with relatively more approvals, including lung and breast cancer, melanoma, lymphoma, and leukemia.
A report from the American Cancer Society (ACS) estimated that, from 1991 to 2017, there were 2,902,200 total cancer deaths avoided from improvements in mortality from all potential sources.
The new findings, reported in the Journal of Medical Economics, suggest that drugs approved between 2000 and 2016 to treat the 15 most common cancer types helped to reduce mortality by 24% per 100,000 people.
“This study provides evidence that a significant share of that reduction from 2000 to 2016 was associated with the introduction of new therapies. The ACS report and other studies demonstrate that the improvements in lung cancer specifically are likely due to new treatments,” said lead study author Joanna P. MacEwan, MD, of PRECISIONheor in Los Angeles.
The findings contribute to a better understanding of whether increased spending on cancer drugs are worth the investment, according to the study authors.
“We provide evidence that the gains in survival measured in clinical trials are translating into health benefits for patients in the real world and confirm previous research that has also shown that new pharmaceutical treatments are associated with improved real-world survival outcomes for patients,” Dr. MacEwan said.
Full effect not yet observed
The researchers used a series of national data sets from sources including the Centers for Disease Control and Prevention; the U.S. Mortality Files by the National Center of Health Statistics; Survival, Epidemiology and End Results program; and United States Cancer Statistics.
The team calculated age-adjusted cancer mortality rates per year for the 15 most common tumor types and also looked at incident cases of cancer by tumor type, represented as per 100,000 people, for all ages, races, and genders.
The researchers then translated the change in cancer mortality in the U.S. from 2000 to 2016 associated with treatment stocks in each year into deaths averted per year.
Across the 16 years, mortality was down by 1,291,769 deaths. The following cancers had significant reductions in mortality: breast (n = 127,874), colorectal (n = 46,705), lung (n = 375,256), prostate (n = 476,210), gastric (n = 758), and renal (n = 739) cancers, as well as non-Hodgkin lymphoma (n = 48,836) and leukemia (n = 4,011).
Estimated mortality increased by 825 deaths in patients with thyroid cancer and 7,768 deaths for those with bladder cancer. These rises are likely due to the result of sparse drug approvals during this period – five for thyroid cancer and three for bladder cancer – Dr. MacEwan said. There were no approvals in liver or uterine cancer and few approvals in pancreatic and oral cancer.
The full effect of new drug introductions may not have been observed yet, Dr. MacEwan noted.
“There are fewer patients using the treatments for drugs approved in the later years of our study and less follow-up time to measure outcomes,” she said. “Over time, utilization of the newer therapies will likely increase and the full effect on mortality will be observed.”
Other factors at play
Multiple factors have led to the declines in mortality, said William G. Cance, MD, chief medical and scientific officer for the ACS, who was not involved in this study. “We are slowly sorting out the explanations in greater granularity.”
Dr. MacEwan said improved cancer screening may partially explain the decline in mortality in some tumor types.
“If screening in a particular tumor type improved during the study period and tumors were diagnosed earlier, then mortality for that tumor type may decline,” she said. “However, we did not find strong evidence to suggest that there were significant changes in screening during our study period. Breast cancer screening rates, for example, were stable over our study period.”
Cancer screening is not as strong an influence as it should be, Dr. Cance said.
“The lung cancer screening rate is low. In breast and colorectal cancers, we need to double down on earlier screening,” he said, noting that less than one-quarter of adults between ages 45 and 50 years are currently screened for colorectal cancer. The ACS recommends that people at average risk of colorectal cancer start regular screening at age 45.
More research is necessary to evaluate the relationship between drug approvals and cancer mortality, Dr. MacEwan said.
“Research directly linking utilization of new therapies to improved survival or reduced mortality in the real-world setting would more definitively demonstrate the impact of new treatments,” she said. “New therapies have improved outcomes for many patients and should continue to be considered as key elements of cancer treatment.”
“We need to continue to reduce tobacco smoking and improve on modifiable behaviors at the same time as we work on getting new drugs to cancer patients,” Dr. Cance said. “We are coming into an era of multiple new therapeutics, including targeted therapies, immunotherapies, and cellular therapies. Clinicians need to look closely at the trial data of new drugs and pay close attention to those that have the most mortality impact.”
“We also need equitable distribution of newer drugs,” Dr. Cance added. “They should be distributed to everybody who deserves them. Mortality is often impacted by social determinants of health.”
Funding for this research was provided by Pfizer. Study authors disclosed relationships, including employment, with Pfizer. Dr. Cance had no disclosures.
SOURCE: MacEwan JP et al. J Med Econ. 2020 Nov 9;1-12.
FROM JOURNAL OF MEDICAL ECONOMICS
‘Test all patients with cancer’: One in eight have inherited mutations
These findings come from the largest study of its kind so far, conducted in nearly 3,000 patients with a wide range of cancer stages and types, including breast, colorectal, lung, ovarian, pancreatic, bladder, prostate, and endometrial cancers.
“This study tells us that the clinical practice guidelines are not very sensitive for identifying who does or doesn’t have a genetic mutation that is predisposing them to cancer,” commented first author Niloy Jewell Samadder, MD, director of the high-risk cancer clinic at the Mayo Clinic in Phoenix.
Finding a genetic mutation can alter clinical management of the cancer.
“This really does open up treatment and management options that might not have been accessible to these patients,” Dr. Samadder emphasized.
The results were published online on Oct. 30 in JAMA Oncology and were presented simultaneously at the American Society of Human Genetics. Dr. Samadder discussed details of the study in a video posted on YouTube.
A clinician not involved in the study said the new results should lead to changes in practice.
“For cancer patients, I think the debate is over. We should test everybody,” Peter Beitsch, MD, surgical oncologist at the Dallas Surgical Group, said in an interview.
The Mayo Clinic is changing its daily practice at all four of its cancer centers. The changes will begin in the first quarter of 2021 at its Arizona campus.
“Every cancer patient who comes to Mayo Clinic will be offered genomic evaluation that includes genetic testing to identify if they have an underlying genetic mutation that predisposes to their cancer and [helps physicians decide] how to incorporate that knowledge into designing the best surgical and treatment options for that patient and their family,” Dr. Samadder said.
Study details
The study included 2,984 patients with cancer who were receiving care for a variety of solid tumor cancers at Mayo Clinic cancer centers in Arizona, Florida, Minnesota, and a community cancer center in Wisconsin.
Patients were tested for about 84 genes using next-generation sequencing provided by Invitae.
Among participants, 13.3% (n = 397) tested positive for pathogenic mutations. Of these, about 70% (282 of 397 patients) carried moderate- and high-penetrance genes that increased their risk for cancer. For almost 28.2% (n = 42) of patients with high-penetrance mutations, changes were made in treatment as a result of genetic testing. These included changes in surgical management, immunotherapy, chemotherapy, or enrollment in a clinical trial for which they may otherwise have not been eligible.
Researchers also compared their universal testing approach with targeted testing recommended in guidelines from the National Comprehensive Cancer Network, the National Society of Genetic Counselors, and the American College of Medical Genetics.
They identified pathogenic mutations in 192 patients whose mutations would have been missed using guideline-recommended criteria, such as tumor pathology or family history. This represents 6.4% of all participants in the study (192 of 2,984 patients) and 48.4% of patients who tested positive for pathogenic mutations (397 of 2,984 patients).
“Genetic testing is underutilized in cancer care, both for patients and for their families, often due to outdated guidelines that restrict testing to a narrow group of high-risk patients. All cancer patients should have access to complete genetic information that can guide their care and inform their families’ health,” coauthor Robert Nussbaum, MD, chief medical officer of Invitae, said in a statement.
Some clinicians have been pushing for genetic testing of all patients with cancer, including Dr. Beitsch, who was lead author of a similar study in breast cancer patients published last year in the Journal of Oncology. That article made waves when the authors concluded that all breast cancer patients should have expanded panel genetic testing.
This new Mayo Clinic study extends the findings in breast cancer to “all cancer patients, not just breast cancer patients,” Dr. Beitsch said in an interview.
Long-running debate
The new findings and opinions add to a long-running debate in oncology over the role of genetic testing and screening for pathogenic mutations.
Part of the debate about genetic testing has hinged on the question of costs, said Dr. Beitsch. When genetic testing first became available, it was conducted by hand, and costs were often prohibitive. Since then, genetic testing has been automated using next-generation sequencing, and the cost has decreased considerably.
“The Invitae cash price for an 80-plus gene panel is $250. That’s [the cost of] a mani-pedi in Dallas. I don’t discount that it’s a lot of money for a lot of people. Yes, it’s expensive, but it’s a lot less expensive than it used to be,” Dr. Beitsch said.
Another issue is that doctors are not entirely sure how to manage variants of uncertain significance (VUSs) when they are found. In the Mayo Clinic study, about half (47.4%; n = 1415) of participants had VUSs. The authors noted that these results are consistent with past studies.
Dr. Beitsch said that VUSs are a matter of education. To date, only about 2% of VUSs have been associated with cancer. The remainder, about 98%, do not affect treatment for patients who have already been diagnosed with cancer.
“We all have VUSs. They’re just minor variations in a gene. The vast majority of them have no consequence and don’t alter the function of the gene,” he said. “I tell everybody to ignore the VUSs [when found in patients with cancer]. Do not act on them at all. We just need to educate everybody to make sure they don’t get stressed about it.”
These comments echo guidance from the American Society of Breast Surgeons, which says that VUSs are DNA sequences that are not clinically actionable. This type of result needs to be considered as inconclusive, and patient management should not be influenced by such results.
However, VUSs are more significant if they are found in individuals who do not have cancer but who have a strong family history of cancer. In such cases, clinicians should be more aware, Dr. Beitsch emphasized.
“Patients who have a VUS and don’t have a cancer should absolutely pay more attention to their health. They got tested for a reason, and that reason is usually strong family history,” Dr. Beitsch said.
He added that a major advantage of genetic testing is that it can enable cascade genetic testing of family members. Identifying pathogenic mutations in family members can lead them to undergo screening to detect early cancers, and preventive measures can be taken that may be lifesaving.
In the Mayo Clinic study, researchers offered genetic testing to family members of patients who tested positive for a pathogenic mutation. Testing was available free of charge for up to 90 days after a participant tested positive. In addition, family members were shown an educational video.
Nevertheless, only 17.6% (n = 70) of patients with pathogenic mutations had family members who underwent testing. Among these, 45% (79 of 176) of family members who were tested were found to carry pathogenic mutations.
“This really told us that financial barriers are not the only barrier to families understanding and undergoing preventive testing,” Dr. Samadder said. “There are probably a number of other barriers – socioeconomic or emotional – that we have to deal with.”
Genetic testing was provided by Invitae. The study was supported by several grants, including a Mayo Transform the Practice Grant, and by Mayo Clinic’s Center for Individualized Medicine. Two coauthors are employees of Invitae. Dr. Beitsch reported participating in a study 2 years ago that was funded by Invitae. He currently receives no financial support from Invitae. Several authors report receiving fees from one or more of the following companies: Pfizer, Maze Therapeutics, Genome Medical, Astellas, and Merck.
This article first appeared on Medscape.com.
These findings come from the largest study of its kind so far, conducted in nearly 3,000 patients with a wide range of cancer stages and types, including breast, colorectal, lung, ovarian, pancreatic, bladder, prostate, and endometrial cancers.
“This study tells us that the clinical practice guidelines are not very sensitive for identifying who does or doesn’t have a genetic mutation that is predisposing them to cancer,” commented first author Niloy Jewell Samadder, MD, director of the high-risk cancer clinic at the Mayo Clinic in Phoenix.
Finding a genetic mutation can alter clinical management of the cancer.
“This really does open up treatment and management options that might not have been accessible to these patients,” Dr. Samadder emphasized.
The results were published online on Oct. 30 in JAMA Oncology and were presented simultaneously at the American Society of Human Genetics. Dr. Samadder discussed details of the study in a video posted on YouTube.
A clinician not involved in the study said the new results should lead to changes in practice.
“For cancer patients, I think the debate is over. We should test everybody,” Peter Beitsch, MD, surgical oncologist at the Dallas Surgical Group, said in an interview.
The Mayo Clinic is changing its daily practice at all four of its cancer centers. The changes will begin in the first quarter of 2021 at its Arizona campus.
“Every cancer patient who comes to Mayo Clinic will be offered genomic evaluation that includes genetic testing to identify if they have an underlying genetic mutation that predisposes to their cancer and [helps physicians decide] how to incorporate that knowledge into designing the best surgical and treatment options for that patient and their family,” Dr. Samadder said.
Study details
The study included 2,984 patients with cancer who were receiving care for a variety of solid tumor cancers at Mayo Clinic cancer centers in Arizona, Florida, Minnesota, and a community cancer center in Wisconsin.
Patients were tested for about 84 genes using next-generation sequencing provided by Invitae.
Among participants, 13.3% (n = 397) tested positive for pathogenic mutations. Of these, about 70% (282 of 397 patients) carried moderate- and high-penetrance genes that increased their risk for cancer. For almost 28.2% (n = 42) of patients with high-penetrance mutations, changes were made in treatment as a result of genetic testing. These included changes in surgical management, immunotherapy, chemotherapy, or enrollment in a clinical trial for which they may otherwise have not been eligible.
Researchers also compared their universal testing approach with targeted testing recommended in guidelines from the National Comprehensive Cancer Network, the National Society of Genetic Counselors, and the American College of Medical Genetics.
They identified pathogenic mutations in 192 patients whose mutations would have been missed using guideline-recommended criteria, such as tumor pathology or family history. This represents 6.4% of all participants in the study (192 of 2,984 patients) and 48.4% of patients who tested positive for pathogenic mutations (397 of 2,984 patients).
“Genetic testing is underutilized in cancer care, both for patients and for their families, often due to outdated guidelines that restrict testing to a narrow group of high-risk patients. All cancer patients should have access to complete genetic information that can guide their care and inform their families’ health,” coauthor Robert Nussbaum, MD, chief medical officer of Invitae, said in a statement.
Some clinicians have been pushing for genetic testing of all patients with cancer, including Dr. Beitsch, who was lead author of a similar study in breast cancer patients published last year in the Journal of Oncology. That article made waves when the authors concluded that all breast cancer patients should have expanded panel genetic testing.
This new Mayo Clinic study extends the findings in breast cancer to “all cancer patients, not just breast cancer patients,” Dr. Beitsch said in an interview.
Long-running debate
The new findings and opinions add to a long-running debate in oncology over the role of genetic testing and screening for pathogenic mutations.
Part of the debate about genetic testing has hinged on the question of costs, said Dr. Beitsch. When genetic testing first became available, it was conducted by hand, and costs were often prohibitive. Since then, genetic testing has been automated using next-generation sequencing, and the cost has decreased considerably.
“The Invitae cash price for an 80-plus gene panel is $250. That’s [the cost of] a mani-pedi in Dallas. I don’t discount that it’s a lot of money for a lot of people. Yes, it’s expensive, but it’s a lot less expensive than it used to be,” Dr. Beitsch said.
Another issue is that doctors are not entirely sure how to manage variants of uncertain significance (VUSs) when they are found. In the Mayo Clinic study, about half (47.4%; n = 1415) of participants had VUSs. The authors noted that these results are consistent with past studies.
Dr. Beitsch said that VUSs are a matter of education. To date, only about 2% of VUSs have been associated with cancer. The remainder, about 98%, do not affect treatment for patients who have already been diagnosed with cancer.
“We all have VUSs. They’re just minor variations in a gene. The vast majority of them have no consequence and don’t alter the function of the gene,” he said. “I tell everybody to ignore the VUSs [when found in patients with cancer]. Do not act on them at all. We just need to educate everybody to make sure they don’t get stressed about it.”
These comments echo guidance from the American Society of Breast Surgeons, which says that VUSs are DNA sequences that are not clinically actionable. This type of result needs to be considered as inconclusive, and patient management should not be influenced by such results.
However, VUSs are more significant if they are found in individuals who do not have cancer but who have a strong family history of cancer. In such cases, clinicians should be more aware, Dr. Beitsch emphasized.
“Patients who have a VUS and don’t have a cancer should absolutely pay more attention to their health. They got tested for a reason, and that reason is usually strong family history,” Dr. Beitsch said.
He added that a major advantage of genetic testing is that it can enable cascade genetic testing of family members. Identifying pathogenic mutations in family members can lead them to undergo screening to detect early cancers, and preventive measures can be taken that may be lifesaving.
In the Mayo Clinic study, researchers offered genetic testing to family members of patients who tested positive for a pathogenic mutation. Testing was available free of charge for up to 90 days after a participant tested positive. In addition, family members were shown an educational video.
Nevertheless, only 17.6% (n = 70) of patients with pathogenic mutations had family members who underwent testing. Among these, 45% (79 of 176) of family members who were tested were found to carry pathogenic mutations.
“This really told us that financial barriers are not the only barrier to families understanding and undergoing preventive testing,” Dr. Samadder said. “There are probably a number of other barriers – socioeconomic or emotional – that we have to deal with.”
Genetic testing was provided by Invitae. The study was supported by several grants, including a Mayo Transform the Practice Grant, and by Mayo Clinic’s Center for Individualized Medicine. Two coauthors are employees of Invitae. Dr. Beitsch reported participating in a study 2 years ago that was funded by Invitae. He currently receives no financial support from Invitae. Several authors report receiving fees from one or more of the following companies: Pfizer, Maze Therapeutics, Genome Medical, Astellas, and Merck.
This article first appeared on Medscape.com.
These findings come from the largest study of its kind so far, conducted in nearly 3,000 patients with a wide range of cancer stages and types, including breast, colorectal, lung, ovarian, pancreatic, bladder, prostate, and endometrial cancers.
“This study tells us that the clinical practice guidelines are not very sensitive for identifying who does or doesn’t have a genetic mutation that is predisposing them to cancer,” commented first author Niloy Jewell Samadder, MD, director of the high-risk cancer clinic at the Mayo Clinic in Phoenix.
Finding a genetic mutation can alter clinical management of the cancer.
“This really does open up treatment and management options that might not have been accessible to these patients,” Dr. Samadder emphasized.
The results were published online on Oct. 30 in JAMA Oncology and were presented simultaneously at the American Society of Human Genetics. Dr. Samadder discussed details of the study in a video posted on YouTube.
A clinician not involved in the study said the new results should lead to changes in practice.
“For cancer patients, I think the debate is over. We should test everybody,” Peter Beitsch, MD, surgical oncologist at the Dallas Surgical Group, said in an interview.
The Mayo Clinic is changing its daily practice at all four of its cancer centers. The changes will begin in the first quarter of 2021 at its Arizona campus.
“Every cancer patient who comes to Mayo Clinic will be offered genomic evaluation that includes genetic testing to identify if they have an underlying genetic mutation that predisposes to their cancer and [helps physicians decide] how to incorporate that knowledge into designing the best surgical and treatment options for that patient and their family,” Dr. Samadder said.
Study details
The study included 2,984 patients with cancer who were receiving care for a variety of solid tumor cancers at Mayo Clinic cancer centers in Arizona, Florida, Minnesota, and a community cancer center in Wisconsin.
Patients were tested for about 84 genes using next-generation sequencing provided by Invitae.
Among participants, 13.3% (n = 397) tested positive for pathogenic mutations. Of these, about 70% (282 of 397 patients) carried moderate- and high-penetrance genes that increased their risk for cancer. For almost 28.2% (n = 42) of patients with high-penetrance mutations, changes were made in treatment as a result of genetic testing. These included changes in surgical management, immunotherapy, chemotherapy, or enrollment in a clinical trial for which they may otherwise have not been eligible.
Researchers also compared their universal testing approach with targeted testing recommended in guidelines from the National Comprehensive Cancer Network, the National Society of Genetic Counselors, and the American College of Medical Genetics.
They identified pathogenic mutations in 192 patients whose mutations would have been missed using guideline-recommended criteria, such as tumor pathology or family history. This represents 6.4% of all participants in the study (192 of 2,984 patients) and 48.4% of patients who tested positive for pathogenic mutations (397 of 2,984 patients).
“Genetic testing is underutilized in cancer care, both for patients and for their families, often due to outdated guidelines that restrict testing to a narrow group of high-risk patients. All cancer patients should have access to complete genetic information that can guide their care and inform their families’ health,” coauthor Robert Nussbaum, MD, chief medical officer of Invitae, said in a statement.
Some clinicians have been pushing for genetic testing of all patients with cancer, including Dr. Beitsch, who was lead author of a similar study in breast cancer patients published last year in the Journal of Oncology. That article made waves when the authors concluded that all breast cancer patients should have expanded panel genetic testing.
This new Mayo Clinic study extends the findings in breast cancer to “all cancer patients, not just breast cancer patients,” Dr. Beitsch said in an interview.
Long-running debate
The new findings and opinions add to a long-running debate in oncology over the role of genetic testing and screening for pathogenic mutations.
Part of the debate about genetic testing has hinged on the question of costs, said Dr. Beitsch. When genetic testing first became available, it was conducted by hand, and costs were often prohibitive. Since then, genetic testing has been automated using next-generation sequencing, and the cost has decreased considerably.
“The Invitae cash price for an 80-plus gene panel is $250. That’s [the cost of] a mani-pedi in Dallas. I don’t discount that it’s a lot of money for a lot of people. Yes, it’s expensive, but it’s a lot less expensive than it used to be,” Dr. Beitsch said.
Another issue is that doctors are not entirely sure how to manage variants of uncertain significance (VUSs) when they are found. In the Mayo Clinic study, about half (47.4%; n = 1415) of participants had VUSs. The authors noted that these results are consistent with past studies.
Dr. Beitsch said that VUSs are a matter of education. To date, only about 2% of VUSs have been associated with cancer. The remainder, about 98%, do not affect treatment for patients who have already been diagnosed with cancer.
“We all have VUSs. They’re just minor variations in a gene. The vast majority of them have no consequence and don’t alter the function of the gene,” he said. “I tell everybody to ignore the VUSs [when found in patients with cancer]. Do not act on them at all. We just need to educate everybody to make sure they don’t get stressed about it.”
These comments echo guidance from the American Society of Breast Surgeons, which says that VUSs are DNA sequences that are not clinically actionable. This type of result needs to be considered as inconclusive, and patient management should not be influenced by such results.
However, VUSs are more significant if they are found in individuals who do not have cancer but who have a strong family history of cancer. In such cases, clinicians should be more aware, Dr. Beitsch emphasized.
“Patients who have a VUS and don’t have a cancer should absolutely pay more attention to their health. They got tested for a reason, and that reason is usually strong family history,” Dr. Beitsch said.
He added that a major advantage of genetic testing is that it can enable cascade genetic testing of family members. Identifying pathogenic mutations in family members can lead them to undergo screening to detect early cancers, and preventive measures can be taken that may be lifesaving.
In the Mayo Clinic study, researchers offered genetic testing to family members of patients who tested positive for a pathogenic mutation. Testing was available free of charge for up to 90 days after a participant tested positive. In addition, family members were shown an educational video.
Nevertheless, only 17.6% (n = 70) of patients with pathogenic mutations had family members who underwent testing. Among these, 45% (79 of 176) of family members who were tested were found to carry pathogenic mutations.
“This really told us that financial barriers are not the only barrier to families understanding and undergoing preventive testing,” Dr. Samadder said. “There are probably a number of other barriers – socioeconomic or emotional – that we have to deal with.”
Genetic testing was provided by Invitae. The study was supported by several grants, including a Mayo Transform the Practice Grant, and by Mayo Clinic’s Center for Individualized Medicine. Two coauthors are employees of Invitae. Dr. Beitsch reported participating in a study 2 years ago that was funded by Invitae. He currently receives no financial support from Invitae. Several authors report receiving fees from one or more of the following companies: Pfizer, Maze Therapeutics, Genome Medical, Astellas, and Merck.
This article first appeared on Medscape.com.
One-month delay in cancer treatment linked to increase in mortality
In light of the treatment delays resulting from the pandemic, Canadian and U.K. researchers carried out a review and analysis of relevant studies published between January 2000 and April 2020.
Included studies examined data on surgical interventions, systemic therapy, or radiotherapy for seven forms of cancer – bladder, breast, colon, rectum, lung, cervix, and head and neck. Delays were measured from diagnosis to the first treatment or from the completion of one treatment to the start of the next.
The search identified 34 suitable studies for 17 indications, with data from more than 1.2 million patients. The analysis identified a significant association between delay and increased mortality for 13 of the 17 indications (P < .05).
For surgery, there was a 6%-8% increase in the risk of death for every 4-week treatment delay. Estimates for systemic treatment varied (hazard ratio range, 1.01-1.28). Four-week delays in radiotherapy were for radical radiotherapy for head and neck cancer (HR, 1.09; 95% confidence interval, 1.05-1.14), adjuvant radiotherapy after breast-conserving surgery (HR, 0.98; 95% CI, 0.88-1.09), and cervical cancer adjuvant radiotherapy (HR, 1.23; 95% CI, 1.00-1.50).
Delays of up to 8 and 12 weeks further increased mortality. An 8-week delay in breast cancer surgery was linked to a 17% increased mortality, and a 12-week delay would increase mortality by 26%.
A surgical delay of 12 weeks for patients with breast cancer continuing for 1 year – which is likely to be the case as the pandemic continues – would lead to 1,400 excess deaths in the United Kingdom.
The authors said the results of this study could be used to guide policy making on the organization of cancer services, particularly as the pandemic continues and further delays are expected.
This article originally appeared on Univadis, part of the Medscape Professional Network.
In light of the treatment delays resulting from the pandemic, Canadian and U.K. researchers carried out a review and analysis of relevant studies published between January 2000 and April 2020.
Included studies examined data on surgical interventions, systemic therapy, or radiotherapy for seven forms of cancer – bladder, breast, colon, rectum, lung, cervix, and head and neck. Delays were measured from diagnosis to the first treatment or from the completion of one treatment to the start of the next.
The search identified 34 suitable studies for 17 indications, with data from more than 1.2 million patients. The analysis identified a significant association between delay and increased mortality for 13 of the 17 indications (P < .05).
For surgery, there was a 6%-8% increase in the risk of death for every 4-week treatment delay. Estimates for systemic treatment varied (hazard ratio range, 1.01-1.28). Four-week delays in radiotherapy were for radical radiotherapy for head and neck cancer (HR, 1.09; 95% confidence interval, 1.05-1.14), adjuvant radiotherapy after breast-conserving surgery (HR, 0.98; 95% CI, 0.88-1.09), and cervical cancer adjuvant radiotherapy (HR, 1.23; 95% CI, 1.00-1.50).
Delays of up to 8 and 12 weeks further increased mortality. An 8-week delay in breast cancer surgery was linked to a 17% increased mortality, and a 12-week delay would increase mortality by 26%.
A surgical delay of 12 weeks for patients with breast cancer continuing for 1 year – which is likely to be the case as the pandemic continues – would lead to 1,400 excess deaths in the United Kingdom.
The authors said the results of this study could be used to guide policy making on the organization of cancer services, particularly as the pandemic continues and further delays are expected.
This article originally appeared on Univadis, part of the Medscape Professional Network.
In light of the treatment delays resulting from the pandemic, Canadian and U.K. researchers carried out a review and analysis of relevant studies published between January 2000 and April 2020.
Included studies examined data on surgical interventions, systemic therapy, or radiotherapy for seven forms of cancer – bladder, breast, colon, rectum, lung, cervix, and head and neck. Delays were measured from diagnosis to the first treatment or from the completion of one treatment to the start of the next.
The search identified 34 suitable studies for 17 indications, with data from more than 1.2 million patients. The analysis identified a significant association between delay and increased mortality for 13 of the 17 indications (P < .05).
For surgery, there was a 6%-8% increase in the risk of death for every 4-week treatment delay. Estimates for systemic treatment varied (hazard ratio range, 1.01-1.28). Four-week delays in radiotherapy were for radical radiotherapy for head and neck cancer (HR, 1.09; 95% confidence interval, 1.05-1.14), adjuvant radiotherapy after breast-conserving surgery (HR, 0.98; 95% CI, 0.88-1.09), and cervical cancer adjuvant radiotherapy (HR, 1.23; 95% CI, 1.00-1.50).
Delays of up to 8 and 12 weeks further increased mortality. An 8-week delay in breast cancer surgery was linked to a 17% increased mortality, and a 12-week delay would increase mortality by 26%.
A surgical delay of 12 weeks for patients with breast cancer continuing for 1 year – which is likely to be the case as the pandemic continues – would lead to 1,400 excess deaths in the United Kingdom.
The authors said the results of this study could be used to guide policy making on the organization of cancer services, particularly as the pandemic continues and further delays are expected.
This article originally appeared on Univadis, part of the Medscape Professional Network.
Pembrolizumab plus axitinib continues to outshine sunitinib for advanced RCC
Pembrolizumab plus axitinib continued to top sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (RCC) in an extended follow-up of the phase 3 KEYNOTE-426 trial.
The trial’s initial results, published in The New England Journal of Medicine in 2019, showed superior efficacy with the combination. Pembrolizumab plus axitinib was subsequently approved in the United States and elsewhere as first-line treatment for advanced RCC.
The latest results from KEYNOTE-426, published in The Lancet Oncology, show a continued survival benefit with pembrolizumab plus axitinib.
“Overall, the results of this study continue to support pembrolizumab plus axitinib as standard of care in patients with previously untreated advanced renal cell carcinoma,” wrote study author Thomas Powles, MD, of the Queen Mary University and Barts Cancer Centre, London, and colleagues.
However, the new findings “must be read and interpreted together with the existing published literature,” they added. This includes trials of nivolumab plus ipilimumab, avelumab plus axitinib, and atezolizumab plus bevacizumab for advanced RCC, all versus sunitinib.
“Given the impossibility of making direct comparisons between the different combinations ... clinical experience and knowledge of the disease and of our patients will be vital to optimize this new therapeutic arsenal and to be able to reach goals that, until a few years ago, were considered unattainable,” wrote authors of a related editorial in The Lancet Oncology.
Trial details and results
KEYNOTE-426 included 861 patients with newly diagnosed stage IV or recurrent metastatic RCC with clear cell histology.
Patients were randomized to sunitinib monotherapy (n = 429) or pembrolizumab plus axitinib (n = 432). Pembrolizumab was given at 200 mg intravenously every 3 weeks for up to 35 cycles, and axitinib was given at 5 mg orally twice daily. Sunitinib was given at 50 mg orally once daily for 4 weeks per 6-week cycle.
Baseline characteristics were similar between the treatment arms. The median age was 62 years in the combination arm and 61 years in the sunitinib arm. Most patients were men (71% and 75%, respectively).
At a median follow-up of 30.6 months, the median overall survival (OS) was 35.7 months in the sunitinib arm but not yet reached in the pembrolizumab-axitinib arm (hazard ratio, 0.68, 95% confidence interval, 0.55-0.85, P = .0003).
The updated hazard ratio for OS with the combination wasn’t as robust as the hazard ratio in the initial analysis (0.53), likely in part because 48% of patients in the sunitinib group subsequently received immunotherapy, according to Dr. Powles and colleagues.
The median progression free survival (PFS) was 11.1 months with sunitinib and 15.4 months with the combination (HR, 0.71, 95% CI, 0.60-0.84, P < .0001). The objective response rate was 60% with pembrolizumab plus axitinib and 40% in the sunitinib group (P < .0001).
Risk groups and response criteria
Although patients in the combination arm had better objective response rates and PFS across all risk categories, there was no OS benefit in the favorable-risk subgroup, perhaps because favorable-risk patients have more indolent disease, Dr. Powles and colleagues noted.
Even so, “the pembrolizumab plus axitinib combination achieved a nonnegligible rate of 11% complete responses in favorable-risk cases, suggesting a potential curative role in this setting,” the editorialists wrote.
Dr. Powles and colleagues raised the question of whether RECIST-defined response is adequate to capture the full benefit of the combination.
In a post hoc analysis, the researchers found that change in tumor size was prognostic for OS. Patients in the pembrolizumab-axitinib group with an “at least 80% reduction in target lesions within 6 months of randomization had a durable subsequent overall survival benefit (i.e., 36 months survival), similar to patients who had RECIST-defined complete response,” Dr. Powles and colleagues wrote.
“These data support a hypothesis that durable benefit to an immunotherapy-containing regimen in renal cell cancer is not limited to the subset of complete responders,” the researchers added. “Because RECIST categories might not classify all patients who achieve durable benefit, depth of response might also supplement objective response as an important clinical endpoint.”
Safety and discontinuation
There were no new safety signals and no new treatment-related deaths.
The most frequent grade 3 or higher adverse events (in the combination and sunitinib arms, respectively) were hypertension (22% and 20%), alanine aminotransferase elevations (13% and 3%), and diarrhea (11% and 5%).
Treatment-related adverse events led to pembrolizumab interruption in 44% of patients, axitinib interruption in 62%, and interruption of both in 30%. Treatment-related adverse events led to discontinuation of one or the other drug in about 20% of subjects and both in 7%.
The number of discontinuations and interruptions suggests “caution in optimizing the therapeutic choice in real-world patients,” the editorialists wrote.
“New treatment modalities, including intermittent administrations or an induction phase followed by single-agent maintenance, could be explored in future adaptive clinical trials, with undeniable advantages in terms of reducing clinical and financial toxicity,” they added.
The KEYNOTE-426 study was funded by Merck, maker of pembrolizumab. The investigators and the editorialists disclosed ties to Merck and other companies.
SOURCE: Powles T et al. Lancet Oncol. 2020 Oct. 23. doi: 10.1016/S1470-2045(20)30436-8.
Pembrolizumab plus axitinib continued to top sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (RCC) in an extended follow-up of the phase 3 KEYNOTE-426 trial.
The trial’s initial results, published in The New England Journal of Medicine in 2019, showed superior efficacy with the combination. Pembrolizumab plus axitinib was subsequently approved in the United States and elsewhere as first-line treatment for advanced RCC.
The latest results from KEYNOTE-426, published in The Lancet Oncology, show a continued survival benefit with pembrolizumab plus axitinib.
“Overall, the results of this study continue to support pembrolizumab plus axitinib as standard of care in patients with previously untreated advanced renal cell carcinoma,” wrote study author Thomas Powles, MD, of the Queen Mary University and Barts Cancer Centre, London, and colleagues.
However, the new findings “must be read and interpreted together with the existing published literature,” they added. This includes trials of nivolumab plus ipilimumab, avelumab plus axitinib, and atezolizumab plus bevacizumab for advanced RCC, all versus sunitinib.
“Given the impossibility of making direct comparisons between the different combinations ... clinical experience and knowledge of the disease and of our patients will be vital to optimize this new therapeutic arsenal and to be able to reach goals that, until a few years ago, were considered unattainable,” wrote authors of a related editorial in The Lancet Oncology.
Trial details and results
KEYNOTE-426 included 861 patients with newly diagnosed stage IV or recurrent metastatic RCC with clear cell histology.
Patients were randomized to sunitinib monotherapy (n = 429) or pembrolizumab plus axitinib (n = 432). Pembrolizumab was given at 200 mg intravenously every 3 weeks for up to 35 cycles, and axitinib was given at 5 mg orally twice daily. Sunitinib was given at 50 mg orally once daily for 4 weeks per 6-week cycle.
Baseline characteristics were similar between the treatment arms. The median age was 62 years in the combination arm and 61 years in the sunitinib arm. Most patients were men (71% and 75%, respectively).
At a median follow-up of 30.6 months, the median overall survival (OS) was 35.7 months in the sunitinib arm but not yet reached in the pembrolizumab-axitinib arm (hazard ratio, 0.68, 95% confidence interval, 0.55-0.85, P = .0003).
The updated hazard ratio for OS with the combination wasn’t as robust as the hazard ratio in the initial analysis (0.53), likely in part because 48% of patients in the sunitinib group subsequently received immunotherapy, according to Dr. Powles and colleagues.
The median progression free survival (PFS) was 11.1 months with sunitinib and 15.4 months with the combination (HR, 0.71, 95% CI, 0.60-0.84, P < .0001). The objective response rate was 60% with pembrolizumab plus axitinib and 40% in the sunitinib group (P < .0001).
Risk groups and response criteria
Although patients in the combination arm had better objective response rates and PFS across all risk categories, there was no OS benefit in the favorable-risk subgroup, perhaps because favorable-risk patients have more indolent disease, Dr. Powles and colleagues noted.
Even so, “the pembrolizumab plus axitinib combination achieved a nonnegligible rate of 11% complete responses in favorable-risk cases, suggesting a potential curative role in this setting,” the editorialists wrote.
Dr. Powles and colleagues raised the question of whether RECIST-defined response is adequate to capture the full benefit of the combination.
In a post hoc analysis, the researchers found that change in tumor size was prognostic for OS. Patients in the pembrolizumab-axitinib group with an “at least 80% reduction in target lesions within 6 months of randomization had a durable subsequent overall survival benefit (i.e., 36 months survival), similar to patients who had RECIST-defined complete response,” Dr. Powles and colleagues wrote.
“These data support a hypothesis that durable benefit to an immunotherapy-containing regimen in renal cell cancer is not limited to the subset of complete responders,” the researchers added. “Because RECIST categories might not classify all patients who achieve durable benefit, depth of response might also supplement objective response as an important clinical endpoint.”
Safety and discontinuation
There were no new safety signals and no new treatment-related deaths.
The most frequent grade 3 or higher adverse events (in the combination and sunitinib arms, respectively) were hypertension (22% and 20%), alanine aminotransferase elevations (13% and 3%), and diarrhea (11% and 5%).
Treatment-related adverse events led to pembrolizumab interruption in 44% of patients, axitinib interruption in 62%, and interruption of both in 30%. Treatment-related adverse events led to discontinuation of one or the other drug in about 20% of subjects and both in 7%.
The number of discontinuations and interruptions suggests “caution in optimizing the therapeutic choice in real-world patients,” the editorialists wrote.
“New treatment modalities, including intermittent administrations or an induction phase followed by single-agent maintenance, could be explored in future adaptive clinical trials, with undeniable advantages in terms of reducing clinical and financial toxicity,” they added.
The KEYNOTE-426 study was funded by Merck, maker of pembrolizumab. The investigators and the editorialists disclosed ties to Merck and other companies.
SOURCE: Powles T et al. Lancet Oncol. 2020 Oct. 23. doi: 10.1016/S1470-2045(20)30436-8.
Pembrolizumab plus axitinib continued to top sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (RCC) in an extended follow-up of the phase 3 KEYNOTE-426 trial.
The trial’s initial results, published in The New England Journal of Medicine in 2019, showed superior efficacy with the combination. Pembrolizumab plus axitinib was subsequently approved in the United States and elsewhere as first-line treatment for advanced RCC.
The latest results from KEYNOTE-426, published in The Lancet Oncology, show a continued survival benefit with pembrolizumab plus axitinib.
“Overall, the results of this study continue to support pembrolizumab plus axitinib as standard of care in patients with previously untreated advanced renal cell carcinoma,” wrote study author Thomas Powles, MD, of the Queen Mary University and Barts Cancer Centre, London, and colleagues.
However, the new findings “must be read and interpreted together with the existing published literature,” they added. This includes trials of nivolumab plus ipilimumab, avelumab plus axitinib, and atezolizumab plus bevacizumab for advanced RCC, all versus sunitinib.
“Given the impossibility of making direct comparisons between the different combinations ... clinical experience and knowledge of the disease and of our patients will be vital to optimize this new therapeutic arsenal and to be able to reach goals that, until a few years ago, were considered unattainable,” wrote authors of a related editorial in The Lancet Oncology.
Trial details and results
KEYNOTE-426 included 861 patients with newly diagnosed stage IV or recurrent metastatic RCC with clear cell histology.
Patients were randomized to sunitinib monotherapy (n = 429) or pembrolizumab plus axitinib (n = 432). Pembrolizumab was given at 200 mg intravenously every 3 weeks for up to 35 cycles, and axitinib was given at 5 mg orally twice daily. Sunitinib was given at 50 mg orally once daily for 4 weeks per 6-week cycle.
Baseline characteristics were similar between the treatment arms. The median age was 62 years in the combination arm and 61 years in the sunitinib arm. Most patients were men (71% and 75%, respectively).
At a median follow-up of 30.6 months, the median overall survival (OS) was 35.7 months in the sunitinib arm but not yet reached in the pembrolizumab-axitinib arm (hazard ratio, 0.68, 95% confidence interval, 0.55-0.85, P = .0003).
The updated hazard ratio for OS with the combination wasn’t as robust as the hazard ratio in the initial analysis (0.53), likely in part because 48% of patients in the sunitinib group subsequently received immunotherapy, according to Dr. Powles and colleagues.
The median progression free survival (PFS) was 11.1 months with sunitinib and 15.4 months with the combination (HR, 0.71, 95% CI, 0.60-0.84, P < .0001). The objective response rate was 60% with pembrolizumab plus axitinib and 40% in the sunitinib group (P < .0001).
Risk groups and response criteria
Although patients in the combination arm had better objective response rates and PFS across all risk categories, there was no OS benefit in the favorable-risk subgroup, perhaps because favorable-risk patients have more indolent disease, Dr. Powles and colleagues noted.
Even so, “the pembrolizumab plus axitinib combination achieved a nonnegligible rate of 11% complete responses in favorable-risk cases, suggesting a potential curative role in this setting,” the editorialists wrote.
Dr. Powles and colleagues raised the question of whether RECIST-defined response is adequate to capture the full benefit of the combination.
In a post hoc analysis, the researchers found that change in tumor size was prognostic for OS. Patients in the pembrolizumab-axitinib group with an “at least 80% reduction in target lesions within 6 months of randomization had a durable subsequent overall survival benefit (i.e., 36 months survival), similar to patients who had RECIST-defined complete response,” Dr. Powles and colleagues wrote.
“These data support a hypothesis that durable benefit to an immunotherapy-containing regimen in renal cell cancer is not limited to the subset of complete responders,” the researchers added. “Because RECIST categories might not classify all patients who achieve durable benefit, depth of response might also supplement objective response as an important clinical endpoint.”
Safety and discontinuation
There were no new safety signals and no new treatment-related deaths.
The most frequent grade 3 or higher adverse events (in the combination and sunitinib arms, respectively) were hypertension (22% and 20%), alanine aminotransferase elevations (13% and 3%), and diarrhea (11% and 5%).
Treatment-related adverse events led to pembrolizumab interruption in 44% of patients, axitinib interruption in 62%, and interruption of both in 30%. Treatment-related adverse events led to discontinuation of one or the other drug in about 20% of subjects and both in 7%.
The number of discontinuations and interruptions suggests “caution in optimizing the therapeutic choice in real-world patients,” the editorialists wrote.
“New treatment modalities, including intermittent administrations or an induction phase followed by single-agent maintenance, could be explored in future adaptive clinical trials, with undeniable advantages in terms of reducing clinical and financial toxicity,” they added.
The KEYNOTE-426 study was funded by Merck, maker of pembrolizumab. The investigators and the editorialists disclosed ties to Merck and other companies.
SOURCE: Powles T et al. Lancet Oncol. 2020 Oct. 23. doi: 10.1016/S1470-2045(20)30436-8.
FROM LANCET ONCOLOGY
No benefit with adjuvant sorafenib in intermediate-/high-risk RCC
“The results of the SORCE trial will end the debate about adjuvant tyrosine kinase inhibitors in renal cell carcinoma for most investigators,” Tim Eisen, MBBChir, PhD, of Cambridge (England) University Hospitals NHS Foundation Trust, said in an interview.
Dr. Eisen and colleagues reported results from SORCE in the Journal of Clinical Oncology.
Patients with intermediate- or high-risk RCC after surgical resection have 5-year relapse rates of 30%-40% and 5-year survival of 74.8% that declines steeply to 16% with metastatic disease, Dr. Eisen and colleagues wrote.
While adjuvant strategies – including cytokines, radiotherapy, and hormone therapy – have not yielded success, oral tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptor have shown efficacy in metastatic RCC.
With inconsistent results in randomized trials of TKIs in the adjuvant RCC setting, however, active surveillance after nephrectomy has remained the international standard of care. SORCE was conducted “to settle the question of adjuvant TKI therapy” in RCC, according to Dr. Eisen and colleagues.
The investigators enrolled 1,711 patients with completely resected, clear cell or non–clear cell RCC at intermediate or high risk of relapse. The patients’ mean age was 58 years, 71% of patients were men, and 84% had clear cell histology.
Patients were randomized (2:3:3) to 3 years of placebo, 1 year of sorafenib followed by 2 years of placebo, or 3 years of sorafenib.
The initial sorafenib dose was 400 mg twice per day orally, but it was amended to 400 mg daily.
The primary outcome was investigator-reported disease-free survival comparing 3 years of sorafenib with placebo.
No survival benefit, more adverse events
Survival outcomes were similar across the study arms. The median disease-free survival was not reached for 3 years of sorafenib or for 3 years of placebo (hazard ratio, 1.01; 95% confidence interval, 0.82-1.23; P = .946).
The restricted mean survival time over 10 years was 6.81 years for 3 years of sorafenib and 6.82 years for 3 years of placebo (P = .988).
As for overall survival, the hazard ratio for 3 years of sorafenib versus 3 years of placebo was 1.06 (95% CI, 0.82-1.38; P = .638), and the hazard ratio for 1 year of sorafenib versus 3 years of placebo was 0.92 (95% CI, 0.71-1.20; P = .541).
Adverse events of grade 3 or higher were reported by 58.6% of patients receiving 1 year of sorafenib, 63.9% of patients receiving 3 years of sorafenib, and 29.2% of patients receiving placebo. Serious adverse events were reported at rates of 19.1% for placebo, 21.6% for 1 year of sorafenib, and 24% for 3 years of sorafenib.
Despite being offered treatment adaptations, more than half of participants had stopped treatment by 12 months because of toxicity.
Results undermine TKI use
“The significant toxicity observed with TKI monotherapy, despite pragmatic dose reductions, together with lack of evidence of a survival benefit, fundamentally undermines the use of TKIs in the adjuvant treatment of RCC,” Dr. Eisen and colleagues concluded.
In an interview, Dr. Eisen noted: “We are now asking whether adjuvant PD-1/PD-L1, with or without CTLA4 checkpoint inhibitors, are of benefit for patients who have had a high- or intermediate-risk RCC resected. A more challenging question is whether neoadjuvant checkpoint inhibitors may add further benefit. There are many such studies, which will report over the next few years and have the potential to change the treatment landscape enormously.”
“Interest in the field in general has shifted to immunotherapy and immunotherapy/TKI combinations,” observed Ramaprasad Srinivasan, MD, PhD, of the National Cancer Institute in Bethesda, Md., who was not involved in this study.
“The majority in the field probably had a fairly good idea that sorafenib was unlikely to show any benefit, whether given over 1 or 3 years. SORCE results were not unexpected. They do cement our belief that TKIs such as sorafenib do not have a real role in managing patients with kidney cancer in the adjuvant setting,” Dr. Srinivasan said.
The SORCE trial was supported by Bayer, Cancer Research UK, the Medical Research Council, University College London, Cancer Australia, and the Australian National Health and Medical Research Council. Dr. Eisen disclosed relationships with AstraZeneca, Roche, EUSA, Bayer, Pfizer, Macmillan Cancer Support, and Kidney Cancer UK. His coauthors disclosed relationships with many companies. Dr. Srinivasan disclosed that the National Cancer Institute has received funds from Calithera Biosciences and Peloton/Merck for clinical trials on which he was the principal investigator.
SOURCE: Eisen T et al. J Clin Oncol. 2020 Oct 14. J Clin Oncol. 2020 Oct 14. doi: 10.1200/JCO.20.01800.
“The results of the SORCE trial will end the debate about adjuvant tyrosine kinase inhibitors in renal cell carcinoma for most investigators,” Tim Eisen, MBBChir, PhD, of Cambridge (England) University Hospitals NHS Foundation Trust, said in an interview.
Dr. Eisen and colleagues reported results from SORCE in the Journal of Clinical Oncology.
Patients with intermediate- or high-risk RCC after surgical resection have 5-year relapse rates of 30%-40% and 5-year survival of 74.8% that declines steeply to 16% with metastatic disease, Dr. Eisen and colleagues wrote.
While adjuvant strategies – including cytokines, radiotherapy, and hormone therapy – have not yielded success, oral tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptor have shown efficacy in metastatic RCC.
With inconsistent results in randomized trials of TKIs in the adjuvant RCC setting, however, active surveillance after nephrectomy has remained the international standard of care. SORCE was conducted “to settle the question of adjuvant TKI therapy” in RCC, according to Dr. Eisen and colleagues.
The investigators enrolled 1,711 patients with completely resected, clear cell or non–clear cell RCC at intermediate or high risk of relapse. The patients’ mean age was 58 years, 71% of patients were men, and 84% had clear cell histology.
Patients were randomized (2:3:3) to 3 years of placebo, 1 year of sorafenib followed by 2 years of placebo, or 3 years of sorafenib.
The initial sorafenib dose was 400 mg twice per day orally, but it was amended to 400 mg daily.
The primary outcome was investigator-reported disease-free survival comparing 3 years of sorafenib with placebo.
No survival benefit, more adverse events
Survival outcomes were similar across the study arms. The median disease-free survival was not reached for 3 years of sorafenib or for 3 years of placebo (hazard ratio, 1.01; 95% confidence interval, 0.82-1.23; P = .946).
The restricted mean survival time over 10 years was 6.81 years for 3 years of sorafenib and 6.82 years for 3 years of placebo (P = .988).
As for overall survival, the hazard ratio for 3 years of sorafenib versus 3 years of placebo was 1.06 (95% CI, 0.82-1.38; P = .638), and the hazard ratio for 1 year of sorafenib versus 3 years of placebo was 0.92 (95% CI, 0.71-1.20; P = .541).
Adverse events of grade 3 or higher were reported by 58.6% of patients receiving 1 year of sorafenib, 63.9% of patients receiving 3 years of sorafenib, and 29.2% of patients receiving placebo. Serious adverse events were reported at rates of 19.1% for placebo, 21.6% for 1 year of sorafenib, and 24% for 3 years of sorafenib.
Despite being offered treatment adaptations, more than half of participants had stopped treatment by 12 months because of toxicity.
Results undermine TKI use
“The significant toxicity observed with TKI monotherapy, despite pragmatic dose reductions, together with lack of evidence of a survival benefit, fundamentally undermines the use of TKIs in the adjuvant treatment of RCC,” Dr. Eisen and colleagues concluded.
In an interview, Dr. Eisen noted: “We are now asking whether adjuvant PD-1/PD-L1, with or without CTLA4 checkpoint inhibitors, are of benefit for patients who have had a high- or intermediate-risk RCC resected. A more challenging question is whether neoadjuvant checkpoint inhibitors may add further benefit. There are many such studies, which will report over the next few years and have the potential to change the treatment landscape enormously.”
“Interest in the field in general has shifted to immunotherapy and immunotherapy/TKI combinations,” observed Ramaprasad Srinivasan, MD, PhD, of the National Cancer Institute in Bethesda, Md., who was not involved in this study.
“The majority in the field probably had a fairly good idea that sorafenib was unlikely to show any benefit, whether given over 1 or 3 years. SORCE results were not unexpected. They do cement our belief that TKIs such as sorafenib do not have a real role in managing patients with kidney cancer in the adjuvant setting,” Dr. Srinivasan said.
The SORCE trial was supported by Bayer, Cancer Research UK, the Medical Research Council, University College London, Cancer Australia, and the Australian National Health and Medical Research Council. Dr. Eisen disclosed relationships with AstraZeneca, Roche, EUSA, Bayer, Pfizer, Macmillan Cancer Support, and Kidney Cancer UK. His coauthors disclosed relationships with many companies. Dr. Srinivasan disclosed that the National Cancer Institute has received funds from Calithera Biosciences and Peloton/Merck for clinical trials on which he was the principal investigator.
SOURCE: Eisen T et al. J Clin Oncol. 2020 Oct 14. J Clin Oncol. 2020 Oct 14. doi: 10.1200/JCO.20.01800.
“The results of the SORCE trial will end the debate about adjuvant tyrosine kinase inhibitors in renal cell carcinoma for most investigators,” Tim Eisen, MBBChir, PhD, of Cambridge (England) University Hospitals NHS Foundation Trust, said in an interview.
Dr. Eisen and colleagues reported results from SORCE in the Journal of Clinical Oncology.
Patients with intermediate- or high-risk RCC after surgical resection have 5-year relapse rates of 30%-40% and 5-year survival of 74.8% that declines steeply to 16% with metastatic disease, Dr. Eisen and colleagues wrote.
While adjuvant strategies – including cytokines, radiotherapy, and hormone therapy – have not yielded success, oral tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptor have shown efficacy in metastatic RCC.
With inconsistent results in randomized trials of TKIs in the adjuvant RCC setting, however, active surveillance after nephrectomy has remained the international standard of care. SORCE was conducted “to settle the question of adjuvant TKI therapy” in RCC, according to Dr. Eisen and colleagues.
The investigators enrolled 1,711 patients with completely resected, clear cell or non–clear cell RCC at intermediate or high risk of relapse. The patients’ mean age was 58 years, 71% of patients were men, and 84% had clear cell histology.
Patients were randomized (2:3:3) to 3 years of placebo, 1 year of sorafenib followed by 2 years of placebo, or 3 years of sorafenib.
The initial sorafenib dose was 400 mg twice per day orally, but it was amended to 400 mg daily.
The primary outcome was investigator-reported disease-free survival comparing 3 years of sorafenib with placebo.
No survival benefit, more adverse events
Survival outcomes were similar across the study arms. The median disease-free survival was not reached for 3 years of sorafenib or for 3 years of placebo (hazard ratio, 1.01; 95% confidence interval, 0.82-1.23; P = .946).
The restricted mean survival time over 10 years was 6.81 years for 3 years of sorafenib and 6.82 years for 3 years of placebo (P = .988).
As for overall survival, the hazard ratio for 3 years of sorafenib versus 3 years of placebo was 1.06 (95% CI, 0.82-1.38; P = .638), and the hazard ratio for 1 year of sorafenib versus 3 years of placebo was 0.92 (95% CI, 0.71-1.20; P = .541).
Adverse events of grade 3 or higher were reported by 58.6% of patients receiving 1 year of sorafenib, 63.9% of patients receiving 3 years of sorafenib, and 29.2% of patients receiving placebo. Serious adverse events were reported at rates of 19.1% for placebo, 21.6% for 1 year of sorafenib, and 24% for 3 years of sorafenib.
Despite being offered treatment adaptations, more than half of participants had stopped treatment by 12 months because of toxicity.
Results undermine TKI use
“The significant toxicity observed with TKI monotherapy, despite pragmatic dose reductions, together with lack of evidence of a survival benefit, fundamentally undermines the use of TKIs in the adjuvant treatment of RCC,” Dr. Eisen and colleagues concluded.
In an interview, Dr. Eisen noted: “We are now asking whether adjuvant PD-1/PD-L1, with or without CTLA4 checkpoint inhibitors, are of benefit for patients who have had a high- or intermediate-risk RCC resected. A more challenging question is whether neoadjuvant checkpoint inhibitors may add further benefit. There are many such studies, which will report over the next few years and have the potential to change the treatment landscape enormously.”
“Interest in the field in general has shifted to immunotherapy and immunotherapy/TKI combinations,” observed Ramaprasad Srinivasan, MD, PhD, of the National Cancer Institute in Bethesda, Md., who was not involved in this study.
“The majority in the field probably had a fairly good idea that sorafenib was unlikely to show any benefit, whether given over 1 or 3 years. SORCE results were not unexpected. They do cement our belief that TKIs such as sorafenib do not have a real role in managing patients with kidney cancer in the adjuvant setting,” Dr. Srinivasan said.
The SORCE trial was supported by Bayer, Cancer Research UK, the Medical Research Council, University College London, Cancer Australia, and the Australian National Health and Medical Research Council. Dr. Eisen disclosed relationships with AstraZeneca, Roche, EUSA, Bayer, Pfizer, Macmillan Cancer Support, and Kidney Cancer UK. His coauthors disclosed relationships with many companies. Dr. Srinivasan disclosed that the National Cancer Institute has received funds from Calithera Biosciences and Peloton/Merck for clinical trials on which he was the principal investigator.
SOURCE: Eisen T et al. J Clin Oncol. 2020 Oct 14. J Clin Oncol. 2020 Oct 14. doi: 10.1200/JCO.20.01800.
FROM THE JOURNAL OF CLINICAL ONCOLOGY