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On improving DLBCL outcomes, single-agent regimens fall short
, a review of the relevant literature suggests.
“In addition ... single-agent regimens are most likely not efficient enough to substantially improve the outcome of patients with DLBCL,” Wendan Xu and colleagues at University Hospital Munster, Germany, concluded, based on their review.
Indeed, novel combinations that include B-cell receptor (BCR) signaling and phosphatidylinositol 3-kinase (PI3K) inhibitors are needed for DLBCL treatment, and treatment should also include conventional chemoimmunotherapeutic regimens as well as other targeted agents and novel immunologic approaches, they wrote. Such novel combinations could overcome mechanisms of resistance and increase cure rates in individuals with DLBCL, they contended.
The authors’ observations are based on a search of the available data, from which they summarized the “current understanding of BCR signaling with a special focus on the PI3K pathway and its role in the pathogenesis of DLBCL.”
The addition of the anti-CD20 antibody rituximab to the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) significantly improved outcomes for patients with DLBCL, but about a third of patients are not cured by the rituximab-CHOP (R-CHOP) regimen and subsequent therapies, they said, explaining their rationale for the review.
“A better understanding of the molecular pathogenesis is warranted to use novel targeted agents in an optimal manner,” they said.
The authors also addressed clinical implications of the findings, and mechanisms of resistance to PI3k inhibitors. For example, they noted that:
–Bruton’s tyrosine kinase (BTK) inhibitors may be beneficial when added to R-CHOP.
In the randomized phase 3 PHOENIX trial, ibrutinib plus R-CHOP versus R-CHOP alone in patients with non–germinal center B-cell (non-GCB) DLBCL showed a survival benefit in patients over 60 years of age, which suggests a possible role for “an intensified R-CHOP regimen that includes a BTK inhibitor” in these patients, they said. They added that confirmatory trials are under way, including the ESCALADE trial looking at the second-generation BTK inhibitor acalabrutinib combined with R-CHOP versus R-CHOP alone in patients with untreated DLBCL.
–Results have been mixed with PI3K inhibitors.
Various PI3K inhibitors have been evaluated for the treatment of patients with DLBCL.
Idelalisib, a first-in-class PI3K-specific inhibitor approved for treatment of relapsed/refractory (r/r) follicular lymphoma, small lymphocytic lymphoma, and chronic lymphocytic leukemia (CLL), showed only modest activity in preclinical DLBCL models, and no responses were detectable in a small trial of patients with r/r DLBCL, the authors said. “Severe toxic side effects and treatment-related deaths occurred in several clinical trials that tested idelalisib in combination with antibodies alone or with antibodies and chemotherapy, leading to the premature discontinuation of some of these studies,” they noted.
Other studies investigating idelalisib plus lenalidomide and rituximab or the spleen tyrosine kinase (SYK) inhibitor entospletinib in patients with r/r CLL or lymphoma were also halted because of “overwhelming, immune-mediated pulmonary and/or hepatic toxicities.”
Copanlisib, an intravenous pan-class I PI3K inhibitor with preferential inhibition of PI3Ka and PI3Kd, showed some promise as monotherapy in a phase 2 trial of patients with r/r DLBCL. The overall response rate was about 20%, and response was “numerically higher” in activated B-cell like (ABC) DLBCL, compared with GCB DLBCL (32% vs. 13%), confirming preclinical data that showed PI3Ka/d inhibition effectiveness mainly in ABC DLBCL.
“Compared with idelalisib, copanlisib appears to have a more favorable toxicity profile, with a lower incidence of severe complications,” they said, adding that a phase 2 trial of copanlisib plus R-CHOP as first-line therapy for patients with DLBCL is under way.
Further, monotherapy with buparlisib, a pan-class I PI3K inhibitor, was associated with a low response rate of 11.5% in a DLBCL subcohort in a phase 2 study, whereas parsaclisib, a next-generation inhibitor with specificity to the PI3Kd isoform, showed efficacy as a monotherapy in patients with r/r DLBCL in a phase 2 study (overall response rate, 25.5%), they said, adding that other PI3K inhibitors with additional inhibitory effects are under clinical development.
–Various molecular mechanisms of resistance to PI3K inhibitors have been described preclinically and clinically.
In an unbiased exploratory analysis of samples from patients treated with copanlisib, a 16-gene mutation signature that separated responders from nonresponders was identified, the authors said.
The finding suggests that genetic aberrations dictate response to PI3K inhibitors, they noted.
“This 16-gene signature included TNFAIP3, CREBBP, and PRDM1, which are known to be important in the molecular pathogenesis of DLBCL,” they wrote. A composite score was developed to reflect the numerical presence or absence of mutations in the gene set, they explained, adding that patients with a high composite score had a significantly higher overall response rate and longer progression-free survival than did patients with a lower score.
In addition, idelalisib treatment resulted in a feedback activation of PI3Ka in ABC DLBCL cells.
“This rebound of PI3K activity was overcome by subsequent PI3Ka inhibition in preclinical DLBCL models, further underscoring the necessity of inhibiting both PI3Ka and PI3Kd to achieve responses in ABC DLBCL,” they wrote, adding that “[i]n ABC DLBCL models treated with the PI3Ka/PI3Kd inhibitor AZD8835, activated CARD11 mutations were identified as a mechanism of resistance.”
Investigations looking at various treatment combinations to overcome resistance to PI3K inhibition and improve the efficacy of targeted approaches are under way, they said.
For example, copanlisib plus the BCL-2 inhibitor venetoclax showed “synergistic activity in BCR-dependent DLBCLs, with genetic bases for BCL-2 dysregulation in vitro and in vivo,” and combination treatment with umbralisib and the proteasome inhibitor carfilzomib showed synergistic cytotoxicity in B-cell lymphoma, they said, noting that the latter combination is currently being evaluated in patients with DLBCL.
This work was supported by a research grant from the Deutsche Krebshilfe. Dr. Xu reported having no financial disclosures.
, a review of the relevant literature suggests.
“In addition ... single-agent regimens are most likely not efficient enough to substantially improve the outcome of patients with DLBCL,” Wendan Xu and colleagues at University Hospital Munster, Germany, concluded, based on their review.
Indeed, novel combinations that include B-cell receptor (BCR) signaling and phosphatidylinositol 3-kinase (PI3K) inhibitors are needed for DLBCL treatment, and treatment should also include conventional chemoimmunotherapeutic regimens as well as other targeted agents and novel immunologic approaches, they wrote. Such novel combinations could overcome mechanisms of resistance and increase cure rates in individuals with DLBCL, they contended.
The authors’ observations are based on a search of the available data, from which they summarized the “current understanding of BCR signaling with a special focus on the PI3K pathway and its role in the pathogenesis of DLBCL.”
The addition of the anti-CD20 antibody rituximab to the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) significantly improved outcomes for patients with DLBCL, but about a third of patients are not cured by the rituximab-CHOP (R-CHOP) regimen and subsequent therapies, they said, explaining their rationale for the review.
“A better understanding of the molecular pathogenesis is warranted to use novel targeted agents in an optimal manner,” they said.
The authors also addressed clinical implications of the findings, and mechanisms of resistance to PI3k inhibitors. For example, they noted that:
–Bruton’s tyrosine kinase (BTK) inhibitors may be beneficial when added to R-CHOP.
In the randomized phase 3 PHOENIX trial, ibrutinib plus R-CHOP versus R-CHOP alone in patients with non–germinal center B-cell (non-GCB) DLBCL showed a survival benefit in patients over 60 years of age, which suggests a possible role for “an intensified R-CHOP regimen that includes a BTK inhibitor” in these patients, they said. They added that confirmatory trials are under way, including the ESCALADE trial looking at the second-generation BTK inhibitor acalabrutinib combined with R-CHOP versus R-CHOP alone in patients with untreated DLBCL.
–Results have been mixed with PI3K inhibitors.
Various PI3K inhibitors have been evaluated for the treatment of patients with DLBCL.
Idelalisib, a first-in-class PI3K-specific inhibitor approved for treatment of relapsed/refractory (r/r) follicular lymphoma, small lymphocytic lymphoma, and chronic lymphocytic leukemia (CLL), showed only modest activity in preclinical DLBCL models, and no responses were detectable in a small trial of patients with r/r DLBCL, the authors said. “Severe toxic side effects and treatment-related deaths occurred in several clinical trials that tested idelalisib in combination with antibodies alone or with antibodies and chemotherapy, leading to the premature discontinuation of some of these studies,” they noted.
Other studies investigating idelalisib plus lenalidomide and rituximab or the spleen tyrosine kinase (SYK) inhibitor entospletinib in patients with r/r CLL or lymphoma were also halted because of “overwhelming, immune-mediated pulmonary and/or hepatic toxicities.”
Copanlisib, an intravenous pan-class I PI3K inhibitor with preferential inhibition of PI3Ka and PI3Kd, showed some promise as monotherapy in a phase 2 trial of patients with r/r DLBCL. The overall response rate was about 20%, and response was “numerically higher” in activated B-cell like (ABC) DLBCL, compared with GCB DLBCL (32% vs. 13%), confirming preclinical data that showed PI3Ka/d inhibition effectiveness mainly in ABC DLBCL.
“Compared with idelalisib, copanlisib appears to have a more favorable toxicity profile, with a lower incidence of severe complications,” they said, adding that a phase 2 trial of copanlisib plus R-CHOP as first-line therapy for patients with DLBCL is under way.
Further, monotherapy with buparlisib, a pan-class I PI3K inhibitor, was associated with a low response rate of 11.5% in a DLBCL subcohort in a phase 2 study, whereas parsaclisib, a next-generation inhibitor with specificity to the PI3Kd isoform, showed efficacy as a monotherapy in patients with r/r DLBCL in a phase 2 study (overall response rate, 25.5%), they said, adding that other PI3K inhibitors with additional inhibitory effects are under clinical development.
–Various molecular mechanisms of resistance to PI3K inhibitors have been described preclinically and clinically.
In an unbiased exploratory analysis of samples from patients treated with copanlisib, a 16-gene mutation signature that separated responders from nonresponders was identified, the authors said.
The finding suggests that genetic aberrations dictate response to PI3K inhibitors, they noted.
“This 16-gene signature included TNFAIP3, CREBBP, and PRDM1, which are known to be important in the molecular pathogenesis of DLBCL,” they wrote. A composite score was developed to reflect the numerical presence or absence of mutations in the gene set, they explained, adding that patients with a high composite score had a significantly higher overall response rate and longer progression-free survival than did patients with a lower score.
In addition, idelalisib treatment resulted in a feedback activation of PI3Ka in ABC DLBCL cells.
“This rebound of PI3K activity was overcome by subsequent PI3Ka inhibition in preclinical DLBCL models, further underscoring the necessity of inhibiting both PI3Ka and PI3Kd to achieve responses in ABC DLBCL,” they wrote, adding that “[i]n ABC DLBCL models treated with the PI3Ka/PI3Kd inhibitor AZD8835, activated CARD11 mutations were identified as a mechanism of resistance.”
Investigations looking at various treatment combinations to overcome resistance to PI3K inhibition and improve the efficacy of targeted approaches are under way, they said.
For example, copanlisib plus the BCL-2 inhibitor venetoclax showed “synergistic activity in BCR-dependent DLBCLs, with genetic bases for BCL-2 dysregulation in vitro and in vivo,” and combination treatment with umbralisib and the proteasome inhibitor carfilzomib showed synergistic cytotoxicity in B-cell lymphoma, they said, noting that the latter combination is currently being evaluated in patients with DLBCL.
This work was supported by a research grant from the Deutsche Krebshilfe. Dr. Xu reported having no financial disclosures.
, a review of the relevant literature suggests.
“In addition ... single-agent regimens are most likely not efficient enough to substantially improve the outcome of patients with DLBCL,” Wendan Xu and colleagues at University Hospital Munster, Germany, concluded, based on their review.
Indeed, novel combinations that include B-cell receptor (BCR) signaling and phosphatidylinositol 3-kinase (PI3K) inhibitors are needed for DLBCL treatment, and treatment should also include conventional chemoimmunotherapeutic regimens as well as other targeted agents and novel immunologic approaches, they wrote. Such novel combinations could overcome mechanisms of resistance and increase cure rates in individuals with DLBCL, they contended.
The authors’ observations are based on a search of the available data, from which they summarized the “current understanding of BCR signaling with a special focus on the PI3K pathway and its role in the pathogenesis of DLBCL.”
The addition of the anti-CD20 antibody rituximab to the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) significantly improved outcomes for patients with DLBCL, but about a third of patients are not cured by the rituximab-CHOP (R-CHOP) regimen and subsequent therapies, they said, explaining their rationale for the review.
“A better understanding of the molecular pathogenesis is warranted to use novel targeted agents in an optimal manner,” they said.
The authors also addressed clinical implications of the findings, and mechanisms of resistance to PI3k inhibitors. For example, they noted that:
–Bruton’s tyrosine kinase (BTK) inhibitors may be beneficial when added to R-CHOP.
In the randomized phase 3 PHOENIX trial, ibrutinib plus R-CHOP versus R-CHOP alone in patients with non–germinal center B-cell (non-GCB) DLBCL showed a survival benefit in patients over 60 years of age, which suggests a possible role for “an intensified R-CHOP regimen that includes a BTK inhibitor” in these patients, they said. They added that confirmatory trials are under way, including the ESCALADE trial looking at the second-generation BTK inhibitor acalabrutinib combined with R-CHOP versus R-CHOP alone in patients with untreated DLBCL.
–Results have been mixed with PI3K inhibitors.
Various PI3K inhibitors have been evaluated for the treatment of patients with DLBCL.
Idelalisib, a first-in-class PI3K-specific inhibitor approved for treatment of relapsed/refractory (r/r) follicular lymphoma, small lymphocytic lymphoma, and chronic lymphocytic leukemia (CLL), showed only modest activity in preclinical DLBCL models, and no responses were detectable in a small trial of patients with r/r DLBCL, the authors said. “Severe toxic side effects and treatment-related deaths occurred in several clinical trials that tested idelalisib in combination with antibodies alone or with antibodies and chemotherapy, leading to the premature discontinuation of some of these studies,” they noted.
Other studies investigating idelalisib plus lenalidomide and rituximab or the spleen tyrosine kinase (SYK) inhibitor entospletinib in patients with r/r CLL or lymphoma were also halted because of “overwhelming, immune-mediated pulmonary and/or hepatic toxicities.”
Copanlisib, an intravenous pan-class I PI3K inhibitor with preferential inhibition of PI3Ka and PI3Kd, showed some promise as monotherapy in a phase 2 trial of patients with r/r DLBCL. The overall response rate was about 20%, and response was “numerically higher” in activated B-cell like (ABC) DLBCL, compared with GCB DLBCL (32% vs. 13%), confirming preclinical data that showed PI3Ka/d inhibition effectiveness mainly in ABC DLBCL.
“Compared with idelalisib, copanlisib appears to have a more favorable toxicity profile, with a lower incidence of severe complications,” they said, adding that a phase 2 trial of copanlisib plus R-CHOP as first-line therapy for patients with DLBCL is under way.
Further, monotherapy with buparlisib, a pan-class I PI3K inhibitor, was associated with a low response rate of 11.5% in a DLBCL subcohort in a phase 2 study, whereas parsaclisib, a next-generation inhibitor with specificity to the PI3Kd isoform, showed efficacy as a monotherapy in patients with r/r DLBCL in a phase 2 study (overall response rate, 25.5%), they said, adding that other PI3K inhibitors with additional inhibitory effects are under clinical development.
–Various molecular mechanisms of resistance to PI3K inhibitors have been described preclinically and clinically.
In an unbiased exploratory analysis of samples from patients treated with copanlisib, a 16-gene mutation signature that separated responders from nonresponders was identified, the authors said.
The finding suggests that genetic aberrations dictate response to PI3K inhibitors, they noted.
“This 16-gene signature included TNFAIP3, CREBBP, and PRDM1, which are known to be important in the molecular pathogenesis of DLBCL,” they wrote. A composite score was developed to reflect the numerical presence or absence of mutations in the gene set, they explained, adding that patients with a high composite score had a significantly higher overall response rate and longer progression-free survival than did patients with a lower score.
In addition, idelalisib treatment resulted in a feedback activation of PI3Ka in ABC DLBCL cells.
“This rebound of PI3K activity was overcome by subsequent PI3Ka inhibition in preclinical DLBCL models, further underscoring the necessity of inhibiting both PI3Ka and PI3Kd to achieve responses in ABC DLBCL,” they wrote, adding that “[i]n ABC DLBCL models treated with the PI3Ka/PI3Kd inhibitor AZD8835, activated CARD11 mutations were identified as a mechanism of resistance.”
Investigations looking at various treatment combinations to overcome resistance to PI3K inhibition and improve the efficacy of targeted approaches are under way, they said.
For example, copanlisib plus the BCL-2 inhibitor venetoclax showed “synergistic activity in BCR-dependent DLBCLs, with genetic bases for BCL-2 dysregulation in vitro and in vivo,” and combination treatment with umbralisib and the proteasome inhibitor carfilzomib showed synergistic cytotoxicity in B-cell lymphoma, they said, noting that the latter combination is currently being evaluated in patients with DLBCL.
This work was supported by a research grant from the Deutsche Krebshilfe. Dr. Xu reported having no financial disclosures.
FROM BLOOD
Early mortality falls in advanced ovarian cancer with neoadjuvant chemo
FROM JAMA ONCOLOGY
Cancer centers with a high use of neoadjuvant chemotherapy in patients with advanced-stage epithelial ovarian cancer show similar improvements in median overall survival and larger declines in short-term mortality than in centers with low use of this treatment. This is according to a study published in JAMA Oncology, suggesting that neoadjuvant chemotherapy may be a suitable first-line treatment approach for many patients with advanced-stage ovarian cancer.
“There is considerable variation in practice. Some centers administer neoadjuvant chemotherapy to 75% of patients with advanced ovarian cancers, others use the approach very infrequently,” said Alexander Melamed, MD, MPH, of Columbia University, New York.
“I hope that those clinicians who have been worried about the negative impacts of too frequent administration of neoadjuvant chemotherapy may be reassured by this study and may come to use this good treatment more often.”
Research has shown that, compared with primary cytoreductive surgery, the use of neoadjuvant chemotherapy has similar long-term survival and improved perioperative outcomes in patients with ovarian cancer. While the use of neoadjuvant chemotherapy has increased, many experts continue to recommend upfront surgery as the preferred treatment for these patients.
“In part, these recommendations are based on flawed interpretations of real-world data. Specifically, many observational studies have concluded that upfront surgery results in better survival than neoadjuvant chemotherapy, based on study designs that ignored the fact that patients who receive neoadjuvant chemotherapy in the real word are sicker and have more extensive cancer than those who receive upfront surgery,” Dr. Melamed said.
In this difference-in-differences comparative effectiveness analysis, researchers asked if the difference in adoption of neoadjuvant chemotherapy by U.S. cancer centers for advanced-stage epithelial ovarian cancer was associated with differences in median overall survival and 1-year all-cause mortality.
“By assessing how this divergence in practice impacted patient outcomes we were able to infer how frequent use of neoadjuvant impacts survival in ovarian cancer patients. This study design allowed us to sidestep the problem of selection bias that has plagued many other observational studies in this space,” Dr. Melamed explained.
This observational study included 39,299 women with stage IIIC and IV epithelial ovarian cancer, diagnosed between 2004 and 2015 who were followed to the end of 2018, and treated at one of 664 cancer programs. Patients treated in programs that increased neoadjuvant chemotherapy administration had greater improvements in 1-year mortality (difference-in-differences, −2.1%; 95% confidence interval, −3.7 to −0.5) and equivalent gains in median overall survival (difference-in-differences, 0.9 months; 95% CI, −1.9 to 3.7 months), compared with those treated in programs that used the treatment infrequently.
“For a long time, experts have suggested that the apparent discordance between randomized controlled trials and real-world studies that compare neoadjuvant chemotherapy to upfront surgery for ovarian cancer might mean that the randomized trials are not applicable to real-world practice. What is significant about our findings, is that, when more appropriate study methods are used to analyze the real-world data, the apparent contradiction between real-world and randomized studies is resolved.
“We found that, just as one would guess based on the findings of randomized trials, patients treated in the centers that increased the use of neoadjuvant chemotherapy did not have any decrement in long-term survival, but that short-term mortality did improve more in these centers than in centers that administered neoadjuvant chemotherapy rarely,” she said.
Dr. Melamed said that the findings should “spur a reappraisal” of what clinicians consider the default treatment for women with stage IIIC and IV ovarian cancer.
Taken together with randomized controlled trials, “the evidence may be at a point where it is now time to consider neoadjuvant chemotherapy as the default approach to patients with bulky carcinomatosis, and that primary surgery may be a reasonable alternative for a select group of healthy, young patients with low-volume metastasis.
“Other factors like the route of adjuvant chemotherapy may also need to be considered. However, I believe the belief that aggressive primary debulking is beneficial for most women with advanced ovarian cancer is outdated,” Dr. Melamed said.
No relevant conflicts of interest were reported for this research.
FROM JAMA ONCOLOGY
Cancer centers with a high use of neoadjuvant chemotherapy in patients with advanced-stage epithelial ovarian cancer show similar improvements in median overall survival and larger declines in short-term mortality than in centers with low use of this treatment. This is according to a study published in JAMA Oncology, suggesting that neoadjuvant chemotherapy may be a suitable first-line treatment approach for many patients with advanced-stage ovarian cancer.
“There is considerable variation in practice. Some centers administer neoadjuvant chemotherapy to 75% of patients with advanced ovarian cancers, others use the approach very infrequently,” said Alexander Melamed, MD, MPH, of Columbia University, New York.
“I hope that those clinicians who have been worried about the negative impacts of too frequent administration of neoadjuvant chemotherapy may be reassured by this study and may come to use this good treatment more often.”
Research has shown that, compared with primary cytoreductive surgery, the use of neoadjuvant chemotherapy has similar long-term survival and improved perioperative outcomes in patients with ovarian cancer. While the use of neoadjuvant chemotherapy has increased, many experts continue to recommend upfront surgery as the preferred treatment for these patients.
“In part, these recommendations are based on flawed interpretations of real-world data. Specifically, many observational studies have concluded that upfront surgery results in better survival than neoadjuvant chemotherapy, based on study designs that ignored the fact that patients who receive neoadjuvant chemotherapy in the real word are sicker and have more extensive cancer than those who receive upfront surgery,” Dr. Melamed said.
In this difference-in-differences comparative effectiveness analysis, researchers asked if the difference in adoption of neoadjuvant chemotherapy by U.S. cancer centers for advanced-stage epithelial ovarian cancer was associated with differences in median overall survival and 1-year all-cause mortality.
“By assessing how this divergence in practice impacted patient outcomes we were able to infer how frequent use of neoadjuvant impacts survival in ovarian cancer patients. This study design allowed us to sidestep the problem of selection bias that has plagued many other observational studies in this space,” Dr. Melamed explained.
This observational study included 39,299 women with stage IIIC and IV epithelial ovarian cancer, diagnosed between 2004 and 2015 who were followed to the end of 2018, and treated at one of 664 cancer programs. Patients treated in programs that increased neoadjuvant chemotherapy administration had greater improvements in 1-year mortality (difference-in-differences, −2.1%; 95% confidence interval, −3.7 to −0.5) and equivalent gains in median overall survival (difference-in-differences, 0.9 months; 95% CI, −1.9 to 3.7 months), compared with those treated in programs that used the treatment infrequently.
“For a long time, experts have suggested that the apparent discordance between randomized controlled trials and real-world studies that compare neoadjuvant chemotherapy to upfront surgery for ovarian cancer might mean that the randomized trials are not applicable to real-world practice. What is significant about our findings, is that, when more appropriate study methods are used to analyze the real-world data, the apparent contradiction between real-world and randomized studies is resolved.
“We found that, just as one would guess based on the findings of randomized trials, patients treated in the centers that increased the use of neoadjuvant chemotherapy did not have any decrement in long-term survival, but that short-term mortality did improve more in these centers than in centers that administered neoadjuvant chemotherapy rarely,” she said.
Dr. Melamed said that the findings should “spur a reappraisal” of what clinicians consider the default treatment for women with stage IIIC and IV ovarian cancer.
Taken together with randomized controlled trials, “the evidence may be at a point where it is now time to consider neoadjuvant chemotherapy as the default approach to patients with bulky carcinomatosis, and that primary surgery may be a reasonable alternative for a select group of healthy, young patients with low-volume metastasis.
“Other factors like the route of adjuvant chemotherapy may also need to be considered. However, I believe the belief that aggressive primary debulking is beneficial for most women with advanced ovarian cancer is outdated,” Dr. Melamed said.
No relevant conflicts of interest were reported for this research.
FROM JAMA ONCOLOGY
Cancer centers with a high use of neoadjuvant chemotherapy in patients with advanced-stage epithelial ovarian cancer show similar improvements in median overall survival and larger declines in short-term mortality than in centers with low use of this treatment. This is according to a study published in JAMA Oncology, suggesting that neoadjuvant chemotherapy may be a suitable first-line treatment approach for many patients with advanced-stage ovarian cancer.
“There is considerable variation in practice. Some centers administer neoadjuvant chemotherapy to 75% of patients with advanced ovarian cancers, others use the approach very infrequently,” said Alexander Melamed, MD, MPH, of Columbia University, New York.
“I hope that those clinicians who have been worried about the negative impacts of too frequent administration of neoadjuvant chemotherapy may be reassured by this study and may come to use this good treatment more often.”
Research has shown that, compared with primary cytoreductive surgery, the use of neoadjuvant chemotherapy has similar long-term survival and improved perioperative outcomes in patients with ovarian cancer. While the use of neoadjuvant chemotherapy has increased, many experts continue to recommend upfront surgery as the preferred treatment for these patients.
“In part, these recommendations are based on flawed interpretations of real-world data. Specifically, many observational studies have concluded that upfront surgery results in better survival than neoadjuvant chemotherapy, based on study designs that ignored the fact that patients who receive neoadjuvant chemotherapy in the real word are sicker and have more extensive cancer than those who receive upfront surgery,” Dr. Melamed said.
In this difference-in-differences comparative effectiveness analysis, researchers asked if the difference in adoption of neoadjuvant chemotherapy by U.S. cancer centers for advanced-stage epithelial ovarian cancer was associated with differences in median overall survival and 1-year all-cause mortality.
“By assessing how this divergence in practice impacted patient outcomes we were able to infer how frequent use of neoadjuvant impacts survival in ovarian cancer patients. This study design allowed us to sidestep the problem of selection bias that has plagued many other observational studies in this space,” Dr. Melamed explained.
This observational study included 39,299 women with stage IIIC and IV epithelial ovarian cancer, diagnosed between 2004 and 2015 who were followed to the end of 2018, and treated at one of 664 cancer programs. Patients treated in programs that increased neoadjuvant chemotherapy administration had greater improvements in 1-year mortality (difference-in-differences, −2.1%; 95% confidence interval, −3.7 to −0.5) and equivalent gains in median overall survival (difference-in-differences, 0.9 months; 95% CI, −1.9 to 3.7 months), compared with those treated in programs that used the treatment infrequently.
“For a long time, experts have suggested that the apparent discordance between randomized controlled trials and real-world studies that compare neoadjuvant chemotherapy to upfront surgery for ovarian cancer might mean that the randomized trials are not applicable to real-world practice. What is significant about our findings, is that, when more appropriate study methods are used to analyze the real-world data, the apparent contradiction between real-world and randomized studies is resolved.
“We found that, just as one would guess based on the findings of randomized trials, patients treated in the centers that increased the use of neoadjuvant chemotherapy did not have any decrement in long-term survival, but that short-term mortality did improve more in these centers than in centers that administered neoadjuvant chemotherapy rarely,” she said.
Dr. Melamed said that the findings should “spur a reappraisal” of what clinicians consider the default treatment for women with stage IIIC and IV ovarian cancer.
Taken together with randomized controlled trials, “the evidence may be at a point where it is now time to consider neoadjuvant chemotherapy as the default approach to patients with bulky carcinomatosis, and that primary surgery may be a reasonable alternative for a select group of healthy, young patients with low-volume metastasis.
“Other factors like the route of adjuvant chemotherapy may also need to be considered. However, I believe the belief that aggressive primary debulking is beneficial for most women with advanced ovarian cancer is outdated,” Dr. Melamed said.
No relevant conflicts of interest were reported for this research.
Donafenib shows potential as first-line treatment of advanced hepatocellular carcinoma
“An improvement in the pharmacotherapy of advanced HCC remains a clinical need,” wrote Feng Bi, MD, of Sichuan University, in Chengdu, China, and colleagues.
Liver cancer is one of the most common cancers worldwide, with HCC representing 90% of liver malignancies. HCC most commonly occurs in people with liver disease, particularly in those with chronic hepatitis B and C and although rare, HCC is the ninth leading cause of cancer deaths in the United States. Most patients are diagnosed at the advanced stage with a median survival of 6-8 months. Sorafenib, the standard first-line therapy for advanced HCC, has demonstrated the median OS of 10.7 to 14.7 months. No other monotherapy has shown a significant improvement in OS, compared with sorafenib. Donafenib has shown favorable efficacy and safety in phase 1 studies.
This phase 2-3 trial evaluated the efficacy and safety of first-line donafenib, compared with sorafenib, in 668 Chinese patients with advanced HCC. Patients were randomly assigned to receive twice-daily oral donafenib 0.2 g or sorafenib 0.4 g until intolerable toxicity or disease progression. The primary end point was OS, tested for noninferiority and superiority.
Compared with sorafenib, donafenib significantly prolonged OS, 10.3 and 12.1 months, respectively, (hazard ratio, 95% confidence interval, 0.699-0.988; 0.83; P = .0245), and the superiority criteria for OS were met. Donafenib also presented improved safety and tolerability. Common drug-related adverse events, such as hand-foot skin reactions and diarrhea, and drug-related grade 3 or higher adverse events, occurred in fewer patients receiving donafenib than sorafenib, (38% vs. 50%; P = .0018). The authors noted that this lower frequency in adverse events with donafenib “contributed to improved patient adherence and decreased levels of drug interruption and discontinuation.”
Donafenib is a novel, oral, small-molecule, multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis by inhibiting vascular endothelial growth factor receptors and platelet-derived growth factor receptors, and Raf kinases. It is a derivative of sorafenib and in June 2021, it was approved in China as a treatment for unresectable hepatocellular carcinoma for patients who have not received systemic treatment. It is not yet available in the United States.
“This pivotal head-to-head comparison study is the first to demonstrate noninferiority and superiority of a monotherapy, donafenib, with statistically significant extension in OS over sorafenib for first-line treatment of advanced HCC,” the authors wrote. “Compared with international trials, patients in this study presented with more severe baseline disease states, further emphasizing the positive response observed with donafenib.”
Another study, published in the same issue of the Journal of Clinical Oncology, compared tremelimumab and durvalumab as monotherapies and in combination for patients with unresectable HCC, found that use a single priming dose of tremelimumab combined with durvalumab showed the best benefit-risk profile.
“An improvement in the pharmacotherapy of advanced HCC remains a clinical need,” wrote Feng Bi, MD, of Sichuan University, in Chengdu, China, and colleagues.
Liver cancer is one of the most common cancers worldwide, with HCC representing 90% of liver malignancies. HCC most commonly occurs in people with liver disease, particularly in those with chronic hepatitis B and C and although rare, HCC is the ninth leading cause of cancer deaths in the United States. Most patients are diagnosed at the advanced stage with a median survival of 6-8 months. Sorafenib, the standard first-line therapy for advanced HCC, has demonstrated the median OS of 10.7 to 14.7 months. No other monotherapy has shown a significant improvement in OS, compared with sorafenib. Donafenib has shown favorable efficacy and safety in phase 1 studies.
This phase 2-3 trial evaluated the efficacy and safety of first-line donafenib, compared with sorafenib, in 668 Chinese patients with advanced HCC. Patients were randomly assigned to receive twice-daily oral donafenib 0.2 g or sorafenib 0.4 g until intolerable toxicity or disease progression. The primary end point was OS, tested for noninferiority and superiority.
Compared with sorafenib, donafenib significantly prolonged OS, 10.3 and 12.1 months, respectively, (hazard ratio, 95% confidence interval, 0.699-0.988; 0.83; P = .0245), and the superiority criteria for OS were met. Donafenib also presented improved safety and tolerability. Common drug-related adverse events, such as hand-foot skin reactions and diarrhea, and drug-related grade 3 or higher adverse events, occurred in fewer patients receiving donafenib than sorafenib, (38% vs. 50%; P = .0018). The authors noted that this lower frequency in adverse events with donafenib “contributed to improved patient adherence and decreased levels of drug interruption and discontinuation.”
Donafenib is a novel, oral, small-molecule, multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis by inhibiting vascular endothelial growth factor receptors and platelet-derived growth factor receptors, and Raf kinases. It is a derivative of sorafenib and in June 2021, it was approved in China as a treatment for unresectable hepatocellular carcinoma for patients who have not received systemic treatment. It is not yet available in the United States.
“This pivotal head-to-head comparison study is the first to demonstrate noninferiority and superiority of a monotherapy, donafenib, with statistically significant extension in OS over sorafenib for first-line treatment of advanced HCC,” the authors wrote. “Compared with international trials, patients in this study presented with more severe baseline disease states, further emphasizing the positive response observed with donafenib.”
Another study, published in the same issue of the Journal of Clinical Oncology, compared tremelimumab and durvalumab as monotherapies and in combination for patients with unresectable HCC, found that use a single priming dose of tremelimumab combined with durvalumab showed the best benefit-risk profile.
“An improvement in the pharmacotherapy of advanced HCC remains a clinical need,” wrote Feng Bi, MD, of Sichuan University, in Chengdu, China, and colleagues.
Liver cancer is one of the most common cancers worldwide, with HCC representing 90% of liver malignancies. HCC most commonly occurs in people with liver disease, particularly in those with chronic hepatitis B and C and although rare, HCC is the ninth leading cause of cancer deaths in the United States. Most patients are diagnosed at the advanced stage with a median survival of 6-8 months. Sorafenib, the standard first-line therapy for advanced HCC, has demonstrated the median OS of 10.7 to 14.7 months. No other monotherapy has shown a significant improvement in OS, compared with sorafenib. Donafenib has shown favorable efficacy and safety in phase 1 studies.
This phase 2-3 trial evaluated the efficacy and safety of first-line donafenib, compared with sorafenib, in 668 Chinese patients with advanced HCC. Patients were randomly assigned to receive twice-daily oral donafenib 0.2 g or sorafenib 0.4 g until intolerable toxicity or disease progression. The primary end point was OS, tested for noninferiority and superiority.
Compared with sorafenib, donafenib significantly prolonged OS, 10.3 and 12.1 months, respectively, (hazard ratio, 95% confidence interval, 0.699-0.988; 0.83; P = .0245), and the superiority criteria for OS were met. Donafenib also presented improved safety and tolerability. Common drug-related adverse events, such as hand-foot skin reactions and diarrhea, and drug-related grade 3 or higher adverse events, occurred in fewer patients receiving donafenib than sorafenib, (38% vs. 50%; P = .0018). The authors noted that this lower frequency in adverse events with donafenib “contributed to improved patient adherence and decreased levels of drug interruption and discontinuation.”
Donafenib is a novel, oral, small-molecule, multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis by inhibiting vascular endothelial growth factor receptors and platelet-derived growth factor receptors, and Raf kinases. It is a derivative of sorafenib and in June 2021, it was approved in China as a treatment for unresectable hepatocellular carcinoma for patients who have not received systemic treatment. It is not yet available in the United States.
“This pivotal head-to-head comparison study is the first to demonstrate noninferiority and superiority of a monotherapy, donafenib, with statistically significant extension in OS over sorafenib for first-line treatment of advanced HCC,” the authors wrote. “Compared with international trials, patients in this study presented with more severe baseline disease states, further emphasizing the positive response observed with donafenib.”
Another study, published in the same issue of the Journal of Clinical Oncology, compared tremelimumab and durvalumab as monotherapies and in combination for patients with unresectable HCC, found that use a single priming dose of tremelimumab combined with durvalumab showed the best benefit-risk profile.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Watchful waiting sometimes best for asymptomatic basal cell carcinoma
“Patient preferences, treatment goals, and the option for proceeding with a watchful waiting approach should be discussed as part of personalized shared decision-making,” wrote Marieke van Winden, MD, MSc, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues. “In patients with a limited life expectancy and asymptomatic low-risk tumors, the time to benefit from treatment might exceed life expectancy, and watchful waiting should be discussed as a potentially appropriate approach.”
As little research has been undertaken on watchful waiting in patients with BCC, the expected tumor growth, progression and the chance of developing symptoms while taking this approach are poorly understood. Patients with limited life expectancy might not live long enough to develop BCC symptoms and may benefit more from watchful waiting than active treatment, authors of the study wrote.
This observational cohort study evaluated the reasons for watchful waiting, along with the natural course of 280 BCCs in 89 patients (53% men, median age 83 years) who chose this approach. Patients had one or more untreated BCCs for at least 3 months and the median follow-up was 9 months. The researchers also looked at the reasons for initiating later treatment.
Patient-related factors, including limited life expectancy, comorbidity prioritizations, and frailty, were the most important reasons to choose watchful waiting in 83% of patients, followed by tumor-related factors in 55% of patients. Of the tumors, 47% increased in size. The estimated tumor diameter increase in 1 year was 4.46 mm for infiltrative/micronodular BCCs and 1.06 mm for nodular, superficial, or clinical BCCs. Tumor growth was not associated with initial tumor size and location.
The most common reasons to initiate active treatment were tumor burden, resolved reasons for watchful waiting, and reevaluation of patient-related factors.
“All patients should be followed up regularly to determine whether a watchful waiting approach is still suited and if patients still prefer watchful waiting to reconsider the consequences of refraining from treatment,” the authors wrote.
In an accompanying editorial, Mackenzie R. Wehner, MD, MPhil, of the University of Texas MD Anderson Cancer Center in Houston, said that, while the observational and retrospective design was a limitation of the study, this allowed the authors to observe patients avoiding or delaying treatment for BCC in real clinical practice.
The study “shows that few patients developed new symptoms, and few patients who decided to treat after a delay had more invasive interventions than originally anticipated, an encouraging result as we continue to study the option and hone the details of active surveillance in BCC,” Dr. Wehner wrote. “It is important to note that the authors did not perform actual active surveillance. This study did not prospectively enroll patients and see them in follow-up at set times, nor did it have prespecified end points for recommending treatment.”
“Before evidence-based active surveillance in BCC can become a viable option, prospective studies of active surveillance, with specified follow-up times and clear outcome measures, are needed,” Dr. Wehner wrote.
Dr. van Winden did not report any conflicts of interest.
“Patient preferences, treatment goals, and the option for proceeding with a watchful waiting approach should be discussed as part of personalized shared decision-making,” wrote Marieke van Winden, MD, MSc, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues. “In patients with a limited life expectancy and asymptomatic low-risk tumors, the time to benefit from treatment might exceed life expectancy, and watchful waiting should be discussed as a potentially appropriate approach.”
As little research has been undertaken on watchful waiting in patients with BCC, the expected tumor growth, progression and the chance of developing symptoms while taking this approach are poorly understood. Patients with limited life expectancy might not live long enough to develop BCC symptoms and may benefit more from watchful waiting than active treatment, authors of the study wrote.
This observational cohort study evaluated the reasons for watchful waiting, along with the natural course of 280 BCCs in 89 patients (53% men, median age 83 years) who chose this approach. Patients had one or more untreated BCCs for at least 3 months and the median follow-up was 9 months. The researchers also looked at the reasons for initiating later treatment.
Patient-related factors, including limited life expectancy, comorbidity prioritizations, and frailty, were the most important reasons to choose watchful waiting in 83% of patients, followed by tumor-related factors in 55% of patients. Of the tumors, 47% increased in size. The estimated tumor diameter increase in 1 year was 4.46 mm for infiltrative/micronodular BCCs and 1.06 mm for nodular, superficial, or clinical BCCs. Tumor growth was not associated with initial tumor size and location.
The most common reasons to initiate active treatment were tumor burden, resolved reasons for watchful waiting, and reevaluation of patient-related factors.
“All patients should be followed up regularly to determine whether a watchful waiting approach is still suited and if patients still prefer watchful waiting to reconsider the consequences of refraining from treatment,” the authors wrote.
In an accompanying editorial, Mackenzie R. Wehner, MD, MPhil, of the University of Texas MD Anderson Cancer Center in Houston, said that, while the observational and retrospective design was a limitation of the study, this allowed the authors to observe patients avoiding or delaying treatment for BCC in real clinical practice.
The study “shows that few patients developed new symptoms, and few patients who decided to treat after a delay had more invasive interventions than originally anticipated, an encouraging result as we continue to study the option and hone the details of active surveillance in BCC,” Dr. Wehner wrote. “It is important to note that the authors did not perform actual active surveillance. This study did not prospectively enroll patients and see them in follow-up at set times, nor did it have prespecified end points for recommending treatment.”
“Before evidence-based active surveillance in BCC can become a viable option, prospective studies of active surveillance, with specified follow-up times and clear outcome measures, are needed,” Dr. Wehner wrote.
Dr. van Winden did not report any conflicts of interest.
“Patient preferences, treatment goals, and the option for proceeding with a watchful waiting approach should be discussed as part of personalized shared decision-making,” wrote Marieke van Winden, MD, MSc, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues. “In patients with a limited life expectancy and asymptomatic low-risk tumors, the time to benefit from treatment might exceed life expectancy, and watchful waiting should be discussed as a potentially appropriate approach.”
As little research has been undertaken on watchful waiting in patients with BCC, the expected tumor growth, progression and the chance of developing symptoms while taking this approach are poorly understood. Patients with limited life expectancy might not live long enough to develop BCC symptoms and may benefit more from watchful waiting than active treatment, authors of the study wrote.
This observational cohort study evaluated the reasons for watchful waiting, along with the natural course of 280 BCCs in 89 patients (53% men, median age 83 years) who chose this approach. Patients had one or more untreated BCCs for at least 3 months and the median follow-up was 9 months. The researchers also looked at the reasons for initiating later treatment.
Patient-related factors, including limited life expectancy, comorbidity prioritizations, and frailty, were the most important reasons to choose watchful waiting in 83% of patients, followed by tumor-related factors in 55% of patients. Of the tumors, 47% increased in size. The estimated tumor diameter increase in 1 year was 4.46 mm for infiltrative/micronodular BCCs and 1.06 mm for nodular, superficial, or clinical BCCs. Tumor growth was not associated with initial tumor size and location.
The most common reasons to initiate active treatment were tumor burden, resolved reasons for watchful waiting, and reevaluation of patient-related factors.
“All patients should be followed up regularly to determine whether a watchful waiting approach is still suited and if patients still prefer watchful waiting to reconsider the consequences of refraining from treatment,” the authors wrote.
In an accompanying editorial, Mackenzie R. Wehner, MD, MPhil, of the University of Texas MD Anderson Cancer Center in Houston, said that, while the observational and retrospective design was a limitation of the study, this allowed the authors to observe patients avoiding or delaying treatment for BCC in real clinical practice.
The study “shows that few patients developed new symptoms, and few patients who decided to treat after a delay had more invasive interventions than originally anticipated, an encouraging result as we continue to study the option and hone the details of active surveillance in BCC,” Dr. Wehner wrote. “It is important to note that the authors did not perform actual active surveillance. This study did not prospectively enroll patients and see them in follow-up at set times, nor did it have prespecified end points for recommending treatment.”
“Before evidence-based active surveillance in BCC can become a viable option, prospective studies of active surveillance, with specified follow-up times and clear outcome measures, are needed,” Dr. Wehner wrote.
Dr. van Winden did not report any conflicts of interest.
FROM JAMA DERMATOLOGY
Many patients, doctors unaware of advancements in cancer care
This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.
The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.
When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.
Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.
“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.
After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”
Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.
Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.
He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.
“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.
That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.
For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
Findings from the patient survey
It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.
“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients
The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.
The survey asked them about how immunotherapy works, what it costs, and its side effects.
Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”
Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.
“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.
A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.
“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.
Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
Results of the doctor survey
The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.
Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).
Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.
Both groups of doctors had a hard time estimating the survival of common cancers.
Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.
However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.
“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.
A version of this article first appeared on Medscape.com.
This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.
The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.
When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.
Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.
“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.
After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”
Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.
Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.
He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.
“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.
That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.
For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
Findings from the patient survey
It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.
“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients
The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.
The survey asked them about how immunotherapy works, what it costs, and its side effects.
Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”
Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.
“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.
A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.
“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.
Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
Results of the doctor survey
The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.
Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).
Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.
Both groups of doctors had a hard time estimating the survival of common cancers.
Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.
However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.
“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.
A version of this article first appeared on Medscape.com.
This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.
The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.
When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.
Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.
“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.
After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”
Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.
Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.
He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.
“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.
That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.
For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
Findings from the patient survey
It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.
“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients
The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.
The survey asked them about how immunotherapy works, what it costs, and its side effects.
Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”
Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.
“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.
A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.
“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.
Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
Results of the doctor survey
The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.
Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).
Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.
Both groups of doctors had a hard time estimating the survival of common cancers.
Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.
However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.
“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.
A version of this article first appeared on Medscape.com.
U.S. study finds racial, gender differences in surgical treatment of dermatofibrosarcoma protuberans
.
Current guidelines recommend Mohs micrographic surgery (MMS) as a first-line treatment for dermatofibrosarcoma protuberans, but the procedure may be inaccessible for certain populations and in some geographic areas, wrote Kevin J. Moore, MD, and Michael S. Chang, BA, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues. Wide local excision (WLE) is a less effective option; recurrence rates associated with this treatment are approximately 30% because of incomplete margin assessment, compared with about 3% with MMS, they noted.
In the study, published as a letter in the Journal of the American Academy of Dermatology, the investigators identified 2,370 cases of dermatofibrosarcoma protuberans using data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Registry from 2000 to 2018. The mean age of the patients was 44 years; 55% were women. A total of 539 patients underwent MMS and 1,831 underwent WLE.
Overall, patients in the WLE group were more likely to be younger, male, Black, and single, the researchers noted. Those who had WLE, they added, were “more commonly deceased at study end date, recipients of adjuvant chemotherapy or radiation, and had truncal tumor locations.”
In a multivariate analysis, patients who were non-Hispanic, White, or other races (including American Indian, Alaskan Native, and Pacific Islander), were significantly more likely to undergo MMS compared with Black and Hispanic patients (adjusted odd ratio [aOR], 1.46, 1.66, and 2.42, respectively). Women were also significantly more likely than were men to undergo MMS (aOR, 1.24). Individuals living in the Western part of the United States were significantly more likely to undergo MMS.
The study findings were limited by several factors including the inability to control for insurance status, lack of data on re-excision, and the use of aggregate case data, the researchers noted. However, the results highlight the disparities in use of MMS for dermatofibrosarcoma protuberans, they said.
“Because MMS is associated with significantly improved outcomes, identifying at-risk patient populations and barriers to accessing MMS is essential,” the researchers noted. The results suggest that disparities persist in accessing MMS for many patients, notably Black and Hispanic males, they said. “Further work is necessary to identify mechanisms for increasing access to MMS,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
.
Current guidelines recommend Mohs micrographic surgery (MMS) as a first-line treatment for dermatofibrosarcoma protuberans, but the procedure may be inaccessible for certain populations and in some geographic areas, wrote Kevin J. Moore, MD, and Michael S. Chang, BA, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues. Wide local excision (WLE) is a less effective option; recurrence rates associated with this treatment are approximately 30% because of incomplete margin assessment, compared with about 3% with MMS, they noted.
In the study, published as a letter in the Journal of the American Academy of Dermatology, the investigators identified 2,370 cases of dermatofibrosarcoma protuberans using data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Registry from 2000 to 2018. The mean age of the patients was 44 years; 55% were women. A total of 539 patients underwent MMS and 1,831 underwent WLE.
Overall, patients in the WLE group were more likely to be younger, male, Black, and single, the researchers noted. Those who had WLE, they added, were “more commonly deceased at study end date, recipients of adjuvant chemotherapy or radiation, and had truncal tumor locations.”
In a multivariate analysis, patients who were non-Hispanic, White, or other races (including American Indian, Alaskan Native, and Pacific Islander), were significantly more likely to undergo MMS compared with Black and Hispanic patients (adjusted odd ratio [aOR], 1.46, 1.66, and 2.42, respectively). Women were also significantly more likely than were men to undergo MMS (aOR, 1.24). Individuals living in the Western part of the United States were significantly more likely to undergo MMS.
The study findings were limited by several factors including the inability to control for insurance status, lack of data on re-excision, and the use of aggregate case data, the researchers noted. However, the results highlight the disparities in use of MMS for dermatofibrosarcoma protuberans, they said.
“Because MMS is associated with significantly improved outcomes, identifying at-risk patient populations and barriers to accessing MMS is essential,” the researchers noted. The results suggest that disparities persist in accessing MMS for many patients, notably Black and Hispanic males, they said. “Further work is necessary to identify mechanisms for increasing access to MMS,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
.
Current guidelines recommend Mohs micrographic surgery (MMS) as a first-line treatment for dermatofibrosarcoma protuberans, but the procedure may be inaccessible for certain populations and in some geographic areas, wrote Kevin J. Moore, MD, and Michael S. Chang, BA, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues. Wide local excision (WLE) is a less effective option; recurrence rates associated with this treatment are approximately 30% because of incomplete margin assessment, compared with about 3% with MMS, they noted.
In the study, published as a letter in the Journal of the American Academy of Dermatology, the investigators identified 2,370 cases of dermatofibrosarcoma protuberans using data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Registry from 2000 to 2018. The mean age of the patients was 44 years; 55% were women. A total of 539 patients underwent MMS and 1,831 underwent WLE.
Overall, patients in the WLE group were more likely to be younger, male, Black, and single, the researchers noted. Those who had WLE, they added, were “more commonly deceased at study end date, recipients of adjuvant chemotherapy or radiation, and had truncal tumor locations.”
In a multivariate analysis, patients who were non-Hispanic, White, or other races (including American Indian, Alaskan Native, and Pacific Islander), were significantly more likely to undergo MMS compared with Black and Hispanic patients (adjusted odd ratio [aOR], 1.46, 1.66, and 2.42, respectively). Women were also significantly more likely than were men to undergo MMS (aOR, 1.24). Individuals living in the Western part of the United States were significantly more likely to undergo MMS.
The study findings were limited by several factors including the inability to control for insurance status, lack of data on re-excision, and the use of aggregate case data, the researchers noted. However, the results highlight the disparities in use of MMS for dermatofibrosarcoma protuberans, they said.
“Because MMS is associated with significantly improved outcomes, identifying at-risk patient populations and barriers to accessing MMS is essential,” the researchers noted. The results suggest that disparities persist in accessing MMS for many patients, notably Black and Hispanic males, they said. “Further work is necessary to identify mechanisms for increasing access to MMS,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
FROM JAAD
FDA approval for tisotumab vedotin in advanced cervical cancer
There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.
In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”
“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.
Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
Details of clinical trial data
The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.
The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.
All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.
The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.
The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.
Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.
Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.
The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
Confirmatory trial underway
Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.
The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.
A version of this article first appeared on Medscape.com.
There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.
In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”
“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.
Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
Details of clinical trial data
The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.
The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.
All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.
The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.
The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.
Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.
Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.
The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
Confirmatory trial underway
Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.
The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.
A version of this article first appeared on Medscape.com.
There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.
In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”
“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.
Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
Details of clinical trial data
The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.
The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.
All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.
The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.
The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.
Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.
Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.
The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
Confirmatory trial underway
Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.
The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.
A version of this article first appeared on Medscape.com.
Study supports chemotherapy with immunotherapy for some never-smokers with lung cancer
Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).
However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.
She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.
Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.
The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.
“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.
The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.
Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.
Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.
For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.
The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.
“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.
Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.
Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.
This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.
Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).
However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.
She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.
Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.
The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.
“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.
The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.
Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.
Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.
For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.
The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.
“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.
Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.
Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.
This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.
Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).
However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.
She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.
Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.
The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.
“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.
The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.
Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.
Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.
For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.
The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.
“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.
Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.
Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.
This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.
FROM ESMO 2021
Duty to Assist: Assisting Veterans with Exposures to Hazardous Materials
Community outreach coordinators identified Veterans who were not aware of their entitlement to service-connected benefits. Veterans were also unaware of the importance of adding new presumptive diagnoses to their existing service connection and were unaware of new conditions that were added to the presumptive lists. Many Veterans, unaware of the Agent Orange/Camp Lejeune presumptive conditions, were paying out of pocket for their oncology care. A project was developed between community outreach and oncology to identify, and contact Veterans newly diagnosed with cancers on the presumptive list for Vietnam and Camp Lejeune. The goals for the project were to: Increase presumptive condition awareness, assist Veterans in navigating the VHA, VBA and VSC (Veteran Service Commission) and provide a VA resource for the Veterans for assistance. Oncology team reviewed the cancer registry each month and identified Veterans who served during the Vietnam Era or the Marine Corps and contacted them to screen for military history. If a Veteran met the time and location qualifications, the Veteran was referred to the community outreach coordinators. The coordinators then further screened the Veterans for eligibility, assisted the Veterans in initiating their claims applications and connected the Veterans with their local VSC. At the six month follow up, 74 Veterans had been referred to community outreach, and 16 Veterans had received 100% service connection. It is important to note, the benefits application process can take several months to complete under normal circumstances. Since implementation the project has been revised. The project team developed mailers to alert Veterans of: Potential benefits eligibility, importance for filing claims, contact information for their local VSC and contact information for VA Outreach for additional assistance. Informatics was recruited to assist with identifying Veterans who met the service criteria and providing their addresses. The Veterans identified were then sent mailers, which expedited the process, allowing the project team to reach more Veterans in a shorter timeframe. Since project initiation, 74 Veterans were contacted directly by outreach coordinators, 273 mailers have been sent to potentially eligible Veterans, and 34 have received 100% service connection to date. al center will continue this practice moving forward.
Community outreach coordinators identified Veterans who were not aware of their entitlement to service-connected benefits. Veterans were also unaware of the importance of adding new presumptive diagnoses to their existing service connection and were unaware of new conditions that were added to the presumptive lists. Many Veterans, unaware of the Agent Orange/Camp Lejeune presumptive conditions, were paying out of pocket for their oncology care. A project was developed between community outreach and oncology to identify, and contact Veterans newly diagnosed with cancers on the presumptive list for Vietnam and Camp Lejeune. The goals for the project were to: Increase presumptive condition awareness, assist Veterans in navigating the VHA, VBA and VSC (Veteran Service Commission) and provide a VA resource for the Veterans for assistance. Oncology team reviewed the cancer registry each month and identified Veterans who served during the Vietnam Era or the Marine Corps and contacted them to screen for military history. If a Veteran met the time and location qualifications, the Veteran was referred to the community outreach coordinators. The coordinators then further screened the Veterans for eligibility, assisted the Veterans in initiating their claims applications and connected the Veterans with their local VSC. At the six month follow up, 74 Veterans had been referred to community outreach, and 16 Veterans had received 100% service connection. It is important to note, the benefits application process can take several months to complete under normal circumstances. Since implementation the project has been revised. The project team developed mailers to alert Veterans of: Potential benefits eligibility, importance for filing claims, contact information for their local VSC and contact information for VA Outreach for additional assistance. Informatics was recruited to assist with identifying Veterans who met the service criteria and providing their addresses. The Veterans identified were then sent mailers, which expedited the process, allowing the project team to reach more Veterans in a shorter timeframe. Since project initiation, 74 Veterans were contacted directly by outreach coordinators, 273 mailers have been sent to potentially eligible Veterans, and 34 have received 100% service connection to date. al center will continue this practice moving forward.
Community outreach coordinators identified Veterans who were not aware of their entitlement to service-connected benefits. Veterans were also unaware of the importance of adding new presumptive diagnoses to their existing service connection and were unaware of new conditions that were added to the presumptive lists. Many Veterans, unaware of the Agent Orange/Camp Lejeune presumptive conditions, were paying out of pocket for their oncology care. A project was developed between community outreach and oncology to identify, and contact Veterans newly diagnosed with cancers on the presumptive list for Vietnam and Camp Lejeune. The goals for the project were to: Increase presumptive condition awareness, assist Veterans in navigating the VHA, VBA and VSC (Veteran Service Commission) and provide a VA resource for the Veterans for assistance. Oncology team reviewed the cancer registry each month and identified Veterans who served during the Vietnam Era or the Marine Corps and contacted them to screen for military history. If a Veteran met the time and location qualifications, the Veteran was referred to the community outreach coordinators. The coordinators then further screened the Veterans for eligibility, assisted the Veterans in initiating their claims applications and connected the Veterans with their local VSC. At the six month follow up, 74 Veterans had been referred to community outreach, and 16 Veterans had received 100% service connection. It is important to note, the benefits application process can take several months to complete under normal circumstances. Since implementation the project has been revised. The project team developed mailers to alert Veterans of: Potential benefits eligibility, importance for filing claims, contact information for their local VSC and contact information for VA Outreach for additional assistance. Informatics was recruited to assist with identifying Veterans who met the service criteria and providing their addresses. The Veterans identified were then sent mailers, which expedited the process, allowing the project team to reach more Veterans in a shorter timeframe. Since project initiation, 74 Veterans were contacted directly by outreach coordinators, 273 mailers have been sent to potentially eligible Veterans, and 34 have received 100% service connection to date. al center will continue this practice moving forward.
Should Geriatric Veterans Get Immunotherapy?
Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.
Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.
“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”
Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.
The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.
“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”
Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”
The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”
Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”
The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”
However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”
“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”
She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.
Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”
No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.
Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.
Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.
“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”
Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.
The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.
“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”
Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”
The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”
Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”
The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”
However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”
“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”
She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.
Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”
No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.
Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.
Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.
“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”
Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.
The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.
“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”
Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”
The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”
Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”
The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”
However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”
“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”
She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.
Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”
No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.