Walter Alexander

Researchers writing in JAMA Network Open report that for patients with metastatic clear cell renal cell carcinoma, removing the kidney and its primary tumor is not associated with improved overall survival.

The finding, which was derived using instrumental variable analysis to adjust for bias due to unmeasured variables, is in contradiction to findings from prior observational data sets.

“These observational studies did not account for selection bias related to unmeasured confounding by surgical indication, and as such, their results may not accurately reflect the effectiveness of the intervention,” wrote the authors, led by Nicholas H. Chakiryan, MD, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla.

The primary outcome analysis using conventional adjustments for selection bias in the final study population of 12,766 patients (median age 63 years, 68% male, 88% White) found cytoreductive nephrectomy performed in 5,005 patients (39%) to be associated with a significant overall survival benefit (multivariable Cox proportional hazards regression: hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.47-0.51; propensity score matching: HR, 0.48; 95%CI, 0.46-0.50). Analysis using instrumental variable estimates, however, did not demonstrate an association between cytoreductive nephrectomy and overall survival (HR, 0.92; 95%CI, 0.78-1.09). “This discrepancy likely reflects the fact that surgical indication for cytoreductive nephrectomy is primarily driven by factors that are not commonly measured or available in observational data sets,” wrote Dr. Chakiryan and colleagues.

For metastatic clear cell renal cell carcinoma (ccRCC) surgical candidates lacking poor-risk disease, cytoreductive nephrectomy has been a clinical standard for decades. Several large observational studies conducted during the current postcytokine, tyrosine kinase–inhibiting targeted therapy era have demonstrated that cytoreductive nephrectomy continues to offer substantial overall survival benefit. These studies did not, however, account for selection bias related to unmeasured confounding by surgical indication.

The researchers identified 12,766 cases of ccRCC from the National Cancer Database, which includes more than 70% of incident cancer cases diagnosed in the United States, from Jan. 1, 2006, to Dec. 31, 2016. Their primary objective was to assess the effect of cytoreductive nephrectomy on overall survival for patients with metastatic ccRCC using instrumental variable analysis to adjust for unmeasured confounding and to compare these results with those generated by conventional adjustments for selection bias.

Instrumental variables are used to control for confounding and measurement error in observational studies. In this study, increasing distance to the treating facility was a significant instrumental variable (P < .001), with an increasing proportion of patients undergoing cytoreductive nephrectomy as distance to a facility increased. “It is worth reinforcing that instrumental variable estimates reflect the outcomes of marginal patients in the sample,” the researchers noted. “In this instance, marginal patients are those whose cytoreductive nephrectomy status was primarily associated with their distance to the treating facility. Increasing distance to the treating facility was significantly associated with receipt of a cytoreductive nephrectomy, presumably because patients are more willing to travel to referral centers for complex surgical care with a limited number of visits, as opposed to receipt of systemic therapy that requires frequent visits for an indefinite period and can be effectively administered locally.”

“Consistent with contemporary level 1 evidence, instrumental variable analysis demonstrated that cytoreductive nephrectomy was not associated with improved overall survival for patients with metastatic clear cell renal cell carcinoma,” the authors concluded.

Among limitations of the analysis, they noted that instrumental variable analyses functionally compare marginal patient populations within the overall cohort, potentially limiting the generalizability of the results.

Researchers writing in JAMA Network Open report that for patients with metastatic clear cell renal cell carcinoma, removing the kidney and its primary tumor is not associated with improved overall survival.

The finding, which was derived using instrumental variable analysis to adjust for bias due to unmeasured variables, is in contradiction to findings from prior observational data sets.

“These observational studies did not account for selection bias related to unmeasured confounding by surgical indication, and as such, their results may not accurately reflect the effectiveness of the intervention,” wrote the authors, led by Nicholas H. Chakiryan, MD, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla.

The primary outcome analysis using conventional adjustments for selection bias in the final study population of 12,766 patients (median age 63 years, 68% male, 88% White) found cytoreductive nephrectomy performed in 5,005 patients (39%) to be associated with a significant overall survival benefit (multivariable Cox proportional hazards regression: hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.47-0.51; propensity score matching: HR, 0.48; 95%CI, 0.46-0.50). Analysis using instrumental variable estimates, however, did not demonstrate an association between cytoreductive nephrectomy and overall survival (HR, 0.92; 95%CI, 0.78-1.09). “This discrepancy likely reflects the fact that surgical indication for cytoreductive nephrectomy is primarily driven by factors that are not commonly measured or available in observational data sets,” wrote Dr. Chakiryan and colleagues.

For metastatic clear cell renal cell carcinoma (ccRCC) surgical candidates lacking poor-risk disease, cytoreductive nephrectomy has been a clinical standard for decades. Several large observational studies conducted during the current postcytokine, tyrosine kinase–inhibiting targeted therapy era have demonstrated that cytoreductive nephrectomy continues to offer substantial overall survival benefit. These studies did not, however, account for selection bias related to unmeasured confounding by surgical indication.

The researchers identified 12,766 cases of ccRCC from the National Cancer Database, which includes more than 70% of incident cancer cases diagnosed in the United States, from Jan. 1, 2006, to Dec. 31, 2016. Their primary objective was to assess the effect of cytoreductive nephrectomy on overall survival for patients with metastatic ccRCC using instrumental variable analysis to adjust for unmeasured confounding and to compare these results with those generated by conventional adjustments for selection bias.

Instrumental variables are used to control for confounding and measurement error in observational studies. In this study, increasing distance to the treating facility was a significant instrumental variable (P < .001), with an increasing proportion of patients undergoing cytoreductive nephrectomy as distance to a facility increased. “It is worth reinforcing that instrumental variable estimates reflect the outcomes of marginal patients in the sample,” the researchers noted. “In this instance, marginal patients are those whose cytoreductive nephrectomy status was primarily associated with their distance to the treating facility. Increasing distance to the treating facility was significantly associated with receipt of a cytoreductive nephrectomy, presumably because patients are more willing to travel to referral centers for complex surgical care with a limited number of visits, as opposed to receipt of systemic therapy that requires frequent visits for an indefinite period and can be effectively administered locally.”

“Consistent with contemporary level 1 evidence, instrumental variable analysis demonstrated that cytoreductive nephrectomy was not associated with improved overall survival for patients with metastatic clear cell renal cell carcinoma,” the authors concluded.

Among limitations of the analysis, they noted that instrumental variable analyses functionally compare marginal patient populations within the overall cohort, potentially limiting the generalizability of the results.

Researchers writing in JAMA Network Open report that for patients with metastatic clear cell renal cell carcinoma, removing the kidney and its primary tumor is not associated with improved overall survival.

The finding, which was derived using instrumental variable analysis to adjust for bias due to unmeasured variables, is in contradiction to findings from prior observational data sets.

“These observational studies did not account for selection bias related to unmeasured confounding by surgical indication, and as such, their results may not accurately reflect the effectiveness of the intervention,” wrote the authors, led by Nicholas H. Chakiryan, MD, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla.

The primary outcome analysis using conventional adjustments for selection bias in the final study population of 12,766 patients (median age 63 years, 68% male, 88% White) found cytoreductive nephrectomy performed in 5,005 patients (39%) to be associated with a significant overall survival benefit (multivariable Cox proportional hazards regression: hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.47-0.51; propensity score matching: HR, 0.48; 95%CI, 0.46-0.50). Analysis using instrumental variable estimates, however, did not demonstrate an association between cytoreductive nephrectomy and overall survival (HR, 0.92; 95%CI, 0.78-1.09). “This discrepancy likely reflects the fact that surgical indication for cytoreductive nephrectomy is primarily driven by factors that are not commonly measured or available in observational data sets,” wrote Dr. Chakiryan and colleagues.

For metastatic clear cell renal cell carcinoma (ccRCC) surgical candidates lacking poor-risk disease, cytoreductive nephrectomy has been a clinical standard for decades. Several large observational studies conducted during the current postcytokine, tyrosine kinase–inhibiting targeted therapy era have demonstrated that cytoreductive nephrectomy continues to offer substantial overall survival benefit. These studies did not, however, account for selection bias related to unmeasured confounding by surgical indication.

The researchers identified 12,766 cases of ccRCC from the National Cancer Database, which includes more than 70% of incident cancer cases diagnosed in the United States, from Jan. 1, 2006, to Dec. 31, 2016. Their primary objective was to assess the effect of cytoreductive nephrectomy on overall survival for patients with metastatic ccRCC using instrumental variable analysis to adjust for unmeasured confounding and to compare these results with those generated by conventional adjustments for selection bias.

Instrumental variables are used to control for confounding and measurement error in observational studies. In this study, increasing distance to the treating facility was a significant instrumental variable (P < .001), with an increasing proportion of patients undergoing cytoreductive nephrectomy as distance to a facility increased. “It is worth reinforcing that instrumental variable estimates reflect the outcomes of marginal patients in the sample,” the researchers noted. “In this instance, marginal patients are those whose cytoreductive nephrectomy status was primarily associated with their distance to the treating facility. Increasing distance to the treating facility was significantly associated with receipt of a cytoreductive nephrectomy, presumably because patients are more willing to travel to referral centers for complex surgical care with a limited number of visits, as opposed to receipt of systemic therapy that requires frequent visits for an indefinite period and can be effectively administered locally.”

“Consistent with contemporary level 1 evidence, instrumental variable analysis demonstrated that cytoreductive nephrectomy was not associated with improved overall survival for patients with metastatic clear cell renal cell carcinoma,” the authors concluded.

Among limitations of the analysis, they noted that instrumental variable analyses functionally compare marginal patient populations within the overall cohort, potentially limiting the generalizability of the results.

A large case-control study finds the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is broader than previously determined from prior analyses showing associations with breast, ovarian, prostate, and pancreatic cancers. The finding, published in JAMA Oncology suggests a possible broader clinical relevance for BRCA1 and BRCA2 genetic testing.

Pathogenic variants in BRCA1 were found to be associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer.

“The results suggest the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is likely broader than that determined from previous analysis of largely European ancestry cohorts,” wrote authors who were led by Yukihide Momozawa, DVM, PhD, RIKEN Center for Integrative Medical Sciences, Japan.

“These risk association findings, together with our analysis of an association with family history of cancer and clinical phenotypes, are relevant for developing and adapting guidelines about genetic testing, treatment options, and treatability with PARP [poly adenosine diphosphate-ribose polymerase] inhibitors for each cancer type,” the authors wrote.

Dr. Momozawa and associates conducted a large-scale sequencing study across 14 common cancer types in 63,828 patients (mean age 64 years, 42% female) and 37,086 controls on data drawn from a Japanese nationwide biobank between April 2003 and March 2018. They estimated the risk of each cancer type and determined clinical characteristics associated with pathogenic variant carrier status, while also investigating the utility of family history in detecting patients with pathogenic variants.

Three hundred fifteen pathogenic variants were identified. An odds ratios of greater than 4.0 (with P < 1 × 10−4 as the threshold of significance) for the pathogenic variants were found for biliary tract cancer (OR, 17.4; 95% confidence interval, 5.8-51.9) in BRCA1, esophageal cancer (OR, 5.6; 95% CI, 2.9-11.0) in BRCA2, and gastric cancer (OR, 5.2; 95% CI, 2.6-10.5) in BRCA1, and (OR, 4.7; 95% CI, 3.1-7.1) in BRCA2. Two other cancer types were found to be associated with BRCA1, and four other cancer types with BRCA2. Enrichment of carrier patients was shown in biliary tract, female breast, ovarian, and prostate cancers in accordance with increased numbers of reported cancer types in relatives.

Male patients with breast cancer had a very high carrier frequency of pathogenic variants in BRCA2 (18.9%), but not BRCA1 (1.89%). Patients with ovarian cancer showed the next highest proportion (BRCA1, 4.86%; BRCA2, 3.42%). Frequency exceeding 1% was seen for several other cancer types (two cancer types for BRCA1, four cancer types for BRCA2). More than one cancer types was identified in 4,128 patients (6.3%). Carrier frequency of pathogenic variants in BRCA1 was 0.44% with one cancer type, 0.85% with two cancer types, and 0.69% with three cancer types. It was 0.97%, 1.40%, and 1.74%, respectively, in BRCA2.

“The results of this large-scale registry-based case-control study suggest that pathogenic variants in BRCA1 and BRCA2 were associated with the risk of seven cancer types. These results indicate broader clinical relevance of BRCA1 and BRCA2 genetic testing,” the authors wrote.

PARP inhibitors were developed based on the mechanism in BRCA1 and BRCA2 of homologous recombination repair defects associated with pathogenic variants. PARP inhibitors have been found to have therapeutic efficacy also in pathogenic variants found to be enriched in prostate and pancreatic cancers. While risk for additional cancer types (for example, biliary tract cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, and stomach cancer) has been reported after analyzing family members for the presence of pathogenic variants and performing case-control analyses, evidence for an association with these cancer types has not been considered sufficient for them to be adopted into clinical management guidelines, the authors wrote.

In an interview, Dr. Momozawa said that BRCA1 and BRCA2 genetic testing should be expanded in Japan. “But further studies are needed to reveal how much. If a clinical trial of a PARP inhibitor for these three cancer types reveals its clinical utility, the importance of this expansion will increase.”

Dr. Momozawa and associates state that while their selection of controls without a family history of cancer affects the generalizability of the study results, the estimated cumulative risks were comparable with those based on prospective cohorts, suggesting the study design did not greatly affect the results.

A large case-control study finds the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is broader than previously determined from prior analyses showing associations with breast, ovarian, prostate, and pancreatic cancers. The finding, published in JAMA Oncology suggests a possible broader clinical relevance for BRCA1 and BRCA2 genetic testing.

Pathogenic variants in BRCA1 were found to be associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer.

“The results suggest the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is likely broader than that determined from previous analysis of largely European ancestry cohorts,” wrote authors who were led by Yukihide Momozawa, DVM, PhD, RIKEN Center for Integrative Medical Sciences, Japan.

“These risk association findings, together with our analysis of an association with family history of cancer and clinical phenotypes, are relevant for developing and adapting guidelines about genetic testing, treatment options, and treatability with PARP [poly adenosine diphosphate-ribose polymerase] inhibitors for each cancer type,” the authors wrote.

Dr. Momozawa and associates conducted a large-scale sequencing study across 14 common cancer types in 63,828 patients (mean age 64 years, 42% female) and 37,086 controls on data drawn from a Japanese nationwide biobank between April 2003 and March 2018. They estimated the risk of each cancer type and determined clinical characteristics associated with pathogenic variant carrier status, while also investigating the utility of family history in detecting patients with pathogenic variants.

Three hundred fifteen pathogenic variants were identified. An odds ratios of greater than 4.0 (with P < 1 × 10−4 as the threshold of significance) for the pathogenic variants were found for biliary tract cancer (OR, 17.4; 95% confidence interval, 5.8-51.9) in BRCA1, esophageal cancer (OR, 5.6; 95% CI, 2.9-11.0) in BRCA2, and gastric cancer (OR, 5.2; 95% CI, 2.6-10.5) in BRCA1, and (OR, 4.7; 95% CI, 3.1-7.1) in BRCA2. Two other cancer types were found to be associated with BRCA1, and four other cancer types with BRCA2. Enrichment of carrier patients was shown in biliary tract, female breast, ovarian, and prostate cancers in accordance with increased numbers of reported cancer types in relatives.

Male patients with breast cancer had a very high carrier frequency of pathogenic variants in BRCA2 (18.9%), but not BRCA1 (1.89%). Patients with ovarian cancer showed the next highest proportion (BRCA1, 4.86%; BRCA2, 3.42%). Frequency exceeding 1% was seen for several other cancer types (two cancer types for BRCA1, four cancer types for BRCA2). More than one cancer types was identified in 4,128 patients (6.3%). Carrier frequency of pathogenic variants in BRCA1 was 0.44% with one cancer type, 0.85% with two cancer types, and 0.69% with three cancer types. It was 0.97%, 1.40%, and 1.74%, respectively, in BRCA2.

“The results of this large-scale registry-based case-control study suggest that pathogenic variants in BRCA1 and BRCA2 were associated with the risk of seven cancer types. These results indicate broader clinical relevance of BRCA1 and BRCA2 genetic testing,” the authors wrote.

PARP inhibitors were developed based on the mechanism in BRCA1 and BRCA2 of homologous recombination repair defects associated with pathogenic variants. PARP inhibitors have been found to have therapeutic efficacy also in pathogenic variants found to be enriched in prostate and pancreatic cancers. While risk for additional cancer types (for example, biliary tract cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, and stomach cancer) has been reported after analyzing family members for the presence of pathogenic variants and performing case-control analyses, evidence for an association with these cancer types has not been considered sufficient for them to be adopted into clinical management guidelines, the authors wrote.

In an interview, Dr. Momozawa said that BRCA1 and BRCA2 genetic testing should be expanded in Japan. “But further studies are needed to reveal how much. If a clinical trial of a PARP inhibitor for these three cancer types reveals its clinical utility, the importance of this expansion will increase.”

Dr. Momozawa and associates state that while their selection of controls without a family history of cancer affects the generalizability of the study results, the estimated cumulative risks were comparable with those based on prospective cohorts, suggesting the study design did not greatly affect the results.

A large case-control study finds the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is broader than previously determined from prior analyses showing associations with breast, ovarian, prostate, and pancreatic cancers. The finding, published in JAMA Oncology suggests a possible broader clinical relevance for BRCA1 and BRCA2 genetic testing.

Pathogenic variants in BRCA1 were found to be associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer.

“The results suggest the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is likely broader than that determined from previous analysis of largely European ancestry cohorts,” wrote authors who were led by Yukihide Momozawa, DVM, PhD, RIKEN Center for Integrative Medical Sciences, Japan.

“These risk association findings, together with our analysis of an association with family history of cancer and clinical phenotypes, are relevant for developing and adapting guidelines about genetic testing, treatment options, and treatability with PARP [poly adenosine diphosphate-ribose polymerase] inhibitors for each cancer type,” the authors wrote.

Dr. Momozawa and associates conducted a large-scale sequencing study across 14 common cancer types in 63,828 patients (mean age 64 years, 42% female) and 37,086 controls on data drawn from a Japanese nationwide biobank between April 2003 and March 2018. They estimated the risk of each cancer type and determined clinical characteristics associated with pathogenic variant carrier status, while also investigating the utility of family history in detecting patients with pathogenic variants.

Three hundred fifteen pathogenic variants were identified. An odds ratios of greater than 4.0 (with P < 1 × 10−4 as the threshold of significance) for the pathogenic variants were found for biliary tract cancer (OR, 17.4; 95% confidence interval, 5.8-51.9) in BRCA1, esophageal cancer (OR, 5.6; 95% CI, 2.9-11.0) in BRCA2, and gastric cancer (OR, 5.2; 95% CI, 2.6-10.5) in BRCA1, and (OR, 4.7; 95% CI, 3.1-7.1) in BRCA2. Two other cancer types were found to be associated with BRCA1, and four other cancer types with BRCA2. Enrichment of carrier patients was shown in biliary tract, female breast, ovarian, and prostate cancers in accordance with increased numbers of reported cancer types in relatives.

Male patients with breast cancer had a very high carrier frequency of pathogenic variants in BRCA2 (18.9%), but not BRCA1 (1.89%). Patients with ovarian cancer showed the next highest proportion (BRCA1, 4.86%; BRCA2, 3.42%). Frequency exceeding 1% was seen for several other cancer types (two cancer types for BRCA1, four cancer types for BRCA2). More than one cancer types was identified in 4,128 patients (6.3%). Carrier frequency of pathogenic variants in BRCA1 was 0.44% with one cancer type, 0.85% with two cancer types, and 0.69% with three cancer types. It was 0.97%, 1.40%, and 1.74%, respectively, in BRCA2.

“The results of this large-scale registry-based case-control study suggest that pathogenic variants in BRCA1 and BRCA2 were associated with the risk of seven cancer types. These results indicate broader clinical relevance of BRCA1 and BRCA2 genetic testing,” the authors wrote.

PARP inhibitors were developed based on the mechanism in BRCA1 and BRCA2 of homologous recombination repair defects associated with pathogenic variants. PARP inhibitors have been found to have therapeutic efficacy also in pathogenic variants found to be enriched in prostate and pancreatic cancers. While risk for additional cancer types (for example, biliary tract cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, and stomach cancer) has been reported after analyzing family members for the presence of pathogenic variants and performing case-control analyses, evidence for an association with these cancer types has not been considered sufficient for them to be adopted into clinical management guidelines, the authors wrote.

In an interview, Dr. Momozawa said that BRCA1 and BRCA2 genetic testing should be expanded in Japan. “But further studies are needed to reveal how much. If a clinical trial of a PARP inhibitor for these three cancer types reveals its clinical utility, the importance of this expansion will increase.”

Dr. Momozawa and associates state that while their selection of controls without a family history of cancer affects the generalizability of the study results, the estimated cumulative risks were comparable with those based on prospective cohorts, suggesting the study design did not greatly affect the results.

Only a small number of research clinical trials for cancer drugs actually show benefit in quality of life, according to a study published in JAMA Oncology.

The study found trials that failed to show improved quality of life often reported their quality of life outcomes more favorably. Non–immunotherapy-targeted drugs were found to lead to worse quality of life outcomes more often than did cytotoxic agents. And, while there is an association between quality of life benefit and overall survival, no such association was found with progression-free survival.

“In this study, we evaluated the outcomes of cancer drug trials with regard to patients’ quality of life and found that only a quarter of phase 3 cancer drug trials in the advanced-disease setting demonstrated improved quality of life,” wrote authors who were led by Bishal Gyawali, MD, PhD, of the Cancer Research Institute, Queen’s University, Kingston, Ont.

“Improved quality of life outcomes were associated with improved overall survival but not with improved progression-free survival. Importantly, almost half of the cancer drugs drug trials that showed improved progression-free survival showed no improved overall survival or quality of life (i.e., PFS-only benefit). Some reports included conclusions regarding quality of life (QOL) findings that were not directly supported by the trial data, particularly for inferior or non–statistically significant QOL outcomes, thereby framing the findings in a favorable light or downplaying detrimental effects of the study intervention on QOL. Furthermore, contrary to common perception, inferior QOL outcomes were more common with targeted drugs than cytotoxic drugs. Taken together, these findings have important policy implications,” the authors wrote.

These findings are based on the results of a cohort study of 45 phase 3 research clinical trials of 24,806 patients. Only a small percentage of patients showed QOL benefits. The study found that industry-funded clinical trial reports often framed QOL findings more favorably than was warranted by the data.

The study found improved QOL with experimental agents in 11 of 45 randomized controlled trials (24.4%). Studies that reported improved QOL were more likely to also show improved overall survival as compared with trials in which quality of life was not improved (7 of 11 [64%] versus 10 of 34 [29%] trials). For improved progression-free survival, however, there was no positive association (6 of 11 [55%] trials versus 17 of 34 [50%] trials without improved QOL). Among six trials reporting worsening QOL, three (50%) were trials of targeted drugs. Among 11 trials reporting improved QOL, 6 (55%) were trials of immunotherapy drugs. Among the 34 trials in which QOL was not improved compared with controls, the findings were framed favorably (versus neutrally or negatively) in the abstract or conclusions in 16 (47%), an observation that was statistically significantly associated with industry funding (chi-squared = 6.35; P = .01).

“It is important to clearly understand and communicate the effects of cancer drugs”

To fulfill the obligation to inform patients about proposed treatments, the authors wrote that it is important to clearly understand and communicate the effects of cancer drugs on patient quality of life alongside their effects on overall survival and intermediate end points such as progression-free survival. “Patients with advanced cancer expect treatment to help them live longer or have better lives,” the authors wrote. In that respect, in clinical trials of cancer medicines, overall survival and quality of life are the most important measures. Toxicity profiles and disease progression delays do not reliably predict quality of life, and studies have shown poor correlations between quality of life, overall survival, and progression-free survival. This raises the question of validity of progression-free survival as a surrogate endpoint. “Progression-free survival is meaningless without overall survival or quality of life gains,” Dr. Gyawali said in an interview.

Writing in The Lancet Oncology in March, Dr. Gyawali stated that, because progression free survival “does not directly measure how a patient feels or functions, or how long a patient lives, progression-free survival was not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. However, over the past 2 decades, it has become the most common primary endpoint in oncology clinical trials. We are deeply worried about how the term survival in this phrase can influence clinical practice and patient choices. We propose replacing the phrase progression-free survival with a less ambiguous term: progression-free interval.”

In JAMA Oncology, Dr. Gyawali aimed to elucidate relationships between QOL, overall survival, and progression-free survival, and to assess, as well, how QOL results are framed, especially in industry-sponsored research. When drug trials they analyzed showed no change in QOL but reported that QOL did not worsen or QOL was maintained rather than stating that QOL did not improve, or if there was downplaying of worse QOL outcomes, the study had favorable interpretation, Dr. Gyawali and associates wrote. The expectation of patients receiving cancer drugs would be improved QOL rather than “not worse” QOL, Dr. Gyawali said.

Regarding the finding that QOL outcomes were described as favorable in 47% of trials with unimproved QOL outcomes, Dr. Gyawali said, “the bias in reporting should be corrected by the reviewers and editors of journals. Also, quality of life reporting should be made mandatory. Without unbiased quality of life information, informed decision making on whether or not to use a certain drug is impossible. Patients and physicians need to know that information. Regulators can demand that this should be mandatory in all trials in noncurative settings.”

He remarked further on the worsening QOL in some targeted drug trials, “People tout chemo-free regimens as automatically having better quality of life, but that doesn’t seem to be the case. Targeted drugs can have a severe impact on quality of life, probably due to prolonged duration of side effects. Quality of life should be measured and reported for all drugs.”

Dr. Gyawali and associates noted the limitation in that several studies with negative QOL results are not published at all or are published after a considerable delay, so the present observations may understate the issues that have been raised.

Dr. Gyawali declared that he received no funding and disclosed no conflicts of interest for this study.

Only a small number of research clinical trials for cancer drugs actually show benefit in quality of life, according to a study published in JAMA Oncology.

The study found trials that failed to show improved quality of life often reported their quality of life outcomes more favorably. Non–immunotherapy-targeted drugs were found to lead to worse quality of life outcomes more often than did cytotoxic agents. And, while there is an association between quality of life benefit and overall survival, no such association was found with progression-free survival.

“In this study, we evaluated the outcomes of cancer drug trials with regard to patients’ quality of life and found that only a quarter of phase 3 cancer drug trials in the advanced-disease setting demonstrated improved quality of life,” wrote authors who were led by Bishal Gyawali, MD, PhD, of the Cancer Research Institute, Queen’s University, Kingston, Ont.

“Improved quality of life outcomes were associated with improved overall survival but not with improved progression-free survival. Importantly, almost half of the cancer drugs drug trials that showed improved progression-free survival showed no improved overall survival or quality of life (i.e., PFS-only benefit). Some reports included conclusions regarding quality of life (QOL) findings that were not directly supported by the trial data, particularly for inferior or non–statistically significant QOL outcomes, thereby framing the findings in a favorable light or downplaying detrimental effects of the study intervention on QOL. Furthermore, contrary to common perception, inferior QOL outcomes were more common with targeted drugs than cytotoxic drugs. Taken together, these findings have important policy implications,” the authors wrote.

These findings are based on the results of a cohort study of 45 phase 3 research clinical trials of 24,806 patients. Only a small percentage of patients showed QOL benefits. The study found that industry-funded clinical trial reports often framed QOL findings more favorably than was warranted by the data.

The study found improved QOL with experimental agents in 11 of 45 randomized controlled trials (24.4%). Studies that reported improved QOL were more likely to also show improved overall survival as compared with trials in which quality of life was not improved (7 of 11 [64%] versus 10 of 34 [29%] trials). For improved progression-free survival, however, there was no positive association (6 of 11 [55%] trials versus 17 of 34 [50%] trials without improved QOL). Among six trials reporting worsening QOL, three (50%) were trials of targeted drugs. Among 11 trials reporting improved QOL, 6 (55%) were trials of immunotherapy drugs. Among the 34 trials in which QOL was not improved compared with controls, the findings were framed favorably (versus neutrally or negatively) in the abstract or conclusions in 16 (47%), an observation that was statistically significantly associated with industry funding (chi-squared = 6.35; P = .01).

“It is important to clearly understand and communicate the effects of cancer drugs”

To fulfill the obligation to inform patients about proposed treatments, the authors wrote that it is important to clearly understand and communicate the effects of cancer drugs on patient quality of life alongside their effects on overall survival and intermediate end points such as progression-free survival. “Patients with advanced cancer expect treatment to help them live longer or have better lives,” the authors wrote. In that respect, in clinical trials of cancer medicines, overall survival and quality of life are the most important measures. Toxicity profiles and disease progression delays do not reliably predict quality of life, and studies have shown poor correlations between quality of life, overall survival, and progression-free survival. This raises the question of validity of progression-free survival as a surrogate endpoint. “Progression-free survival is meaningless without overall survival or quality of life gains,” Dr. Gyawali said in an interview.

Writing in The Lancet Oncology in March, Dr. Gyawali stated that, because progression free survival “does not directly measure how a patient feels or functions, or how long a patient lives, progression-free survival was not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. However, over the past 2 decades, it has become the most common primary endpoint in oncology clinical trials. We are deeply worried about how the term survival in this phrase can influence clinical practice and patient choices. We propose replacing the phrase progression-free survival with a less ambiguous term: progression-free interval.”

In JAMA Oncology, Dr. Gyawali aimed to elucidate relationships between QOL, overall survival, and progression-free survival, and to assess, as well, how QOL results are framed, especially in industry-sponsored research. When drug trials they analyzed showed no change in QOL but reported that QOL did not worsen or QOL was maintained rather than stating that QOL did not improve, or if there was downplaying of worse QOL outcomes, the study had favorable interpretation, Dr. Gyawali and associates wrote. The expectation of patients receiving cancer drugs would be improved QOL rather than “not worse” QOL, Dr. Gyawali said.

Regarding the finding that QOL outcomes were described as favorable in 47% of trials with unimproved QOL outcomes, Dr. Gyawali said, “the bias in reporting should be corrected by the reviewers and editors of journals. Also, quality of life reporting should be made mandatory. Without unbiased quality of life information, informed decision making on whether or not to use a certain drug is impossible. Patients and physicians need to know that information. Regulators can demand that this should be mandatory in all trials in noncurative settings.”

He remarked further on the worsening QOL in some targeted drug trials, “People tout chemo-free regimens as automatically having better quality of life, but that doesn’t seem to be the case. Targeted drugs can have a severe impact on quality of life, probably due to prolonged duration of side effects. Quality of life should be measured and reported for all drugs.”

Dr. Gyawali and associates noted the limitation in that several studies with negative QOL results are not published at all or are published after a considerable delay, so the present observations may understate the issues that have been raised.

Dr. Gyawali declared that he received no funding and disclosed no conflicts of interest for this study.

Only a small number of research clinical trials for cancer drugs actually show benefit in quality of life, according to a study published in JAMA Oncology.

The study found trials that failed to show improved quality of life often reported their quality of life outcomes more favorably. Non–immunotherapy-targeted drugs were found to lead to worse quality of life outcomes more often than did cytotoxic agents. And, while there is an association between quality of life benefit and overall survival, no such association was found with progression-free survival.

“In this study, we evaluated the outcomes of cancer drug trials with regard to patients’ quality of life and found that only a quarter of phase 3 cancer drug trials in the advanced-disease setting demonstrated improved quality of life,” wrote authors who were led by Bishal Gyawali, MD, PhD, of the Cancer Research Institute, Queen’s University, Kingston, Ont.

“Improved quality of life outcomes were associated with improved overall survival but not with improved progression-free survival. Importantly, almost half of the cancer drugs drug trials that showed improved progression-free survival showed no improved overall survival or quality of life (i.e., PFS-only benefit). Some reports included conclusions regarding quality of life (QOL) findings that were not directly supported by the trial data, particularly for inferior or non–statistically significant QOL outcomes, thereby framing the findings in a favorable light or downplaying detrimental effects of the study intervention on QOL. Furthermore, contrary to common perception, inferior QOL outcomes were more common with targeted drugs than cytotoxic drugs. Taken together, these findings have important policy implications,” the authors wrote.

These findings are based on the results of a cohort study of 45 phase 3 research clinical trials of 24,806 patients. Only a small percentage of patients showed QOL benefits. The study found that industry-funded clinical trial reports often framed QOL findings more favorably than was warranted by the data.

The study found improved QOL with experimental agents in 11 of 45 randomized controlled trials (24.4%). Studies that reported improved QOL were more likely to also show improved overall survival as compared with trials in which quality of life was not improved (7 of 11 [64%] versus 10 of 34 [29%] trials). For improved progression-free survival, however, there was no positive association (6 of 11 [55%] trials versus 17 of 34 [50%] trials without improved QOL). Among six trials reporting worsening QOL, three (50%) were trials of targeted drugs. Among 11 trials reporting improved QOL, 6 (55%) were trials of immunotherapy drugs. Among the 34 trials in which QOL was not improved compared with controls, the findings were framed favorably (versus neutrally or negatively) in the abstract or conclusions in 16 (47%), an observation that was statistically significantly associated with industry funding (chi-squared = 6.35; P = .01).

“It is important to clearly understand and communicate the effects of cancer drugs”

To fulfill the obligation to inform patients about proposed treatments, the authors wrote that it is important to clearly understand and communicate the effects of cancer drugs on patient quality of life alongside their effects on overall survival and intermediate end points such as progression-free survival. “Patients with advanced cancer expect treatment to help them live longer or have better lives,” the authors wrote. In that respect, in clinical trials of cancer medicines, overall survival and quality of life are the most important measures. Toxicity profiles and disease progression delays do not reliably predict quality of life, and studies have shown poor correlations between quality of life, overall survival, and progression-free survival. This raises the question of validity of progression-free survival as a surrogate endpoint. “Progression-free survival is meaningless without overall survival or quality of life gains,” Dr. Gyawali said in an interview.

Writing in The Lancet Oncology in March, Dr. Gyawali stated that, because progression free survival “does not directly measure how a patient feels or functions, or how long a patient lives, progression-free survival was not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. However, over the past 2 decades, it has become the most common primary endpoint in oncology clinical trials. We are deeply worried about how the term survival in this phrase can influence clinical practice and patient choices. We propose replacing the phrase progression-free survival with a less ambiguous term: progression-free interval.”

In JAMA Oncology, Dr. Gyawali aimed to elucidate relationships between QOL, overall survival, and progression-free survival, and to assess, as well, how QOL results are framed, especially in industry-sponsored research. When drug trials they analyzed showed no change in QOL but reported that QOL did not worsen or QOL was maintained rather than stating that QOL did not improve, or if there was downplaying of worse QOL outcomes, the study had favorable interpretation, Dr. Gyawali and associates wrote. The expectation of patients receiving cancer drugs would be improved QOL rather than “not worse” QOL, Dr. Gyawali said.

Regarding the finding that QOL outcomes were described as favorable in 47% of trials with unimproved QOL outcomes, Dr. Gyawali said, “the bias in reporting should be corrected by the reviewers and editors of journals. Also, quality of life reporting should be made mandatory. Without unbiased quality of life information, informed decision making on whether or not to use a certain drug is impossible. Patients and physicians need to know that information. Regulators can demand that this should be mandatory in all trials in noncurative settings.”

He remarked further on the worsening QOL in some targeted drug trials, “People tout chemo-free regimens as automatically having better quality of life, but that doesn’t seem to be the case. Targeted drugs can have a severe impact on quality of life, probably due to prolonged duration of side effects. Quality of life should be measured and reported for all drugs.”

Dr. Gyawali and associates noted the limitation in that several studies with negative QOL results are not published at all or are published after a considerable delay, so the present observations may understate the issues that have been raised.

Dr. Gyawali declared that he received no funding and disclosed no conflicts of interest for this study.

Findings from a cohort study highlight a potential role of tumor grade for predicting mucosal head and neck squamous cell carcinoma response to immunotherapy, researchers report in JAMA Otolaryngology–Head & Neck Surgery.

The analysis, which was among patients with either high-grade or low-grade recurrent or metastatic mucosal head and neck squamous cell carcinoma (HNSCC) tumors, revealed that tumor grade was independently associated with immunotherapy response.

“Generally, one would expect high-grade tumors to do worse because they are more aggressive,” said Rajarsi Mandal, MD, the study’s lead author. “But it’s thought that high-grade tumors have higher degrees of chromosomal instability with a lot more mutations generated throughout the genome of these tumors ... and we know that higher mutation rates correlate with higher responses to immunotherapy.”

Researchers found that the proportion of patients having a beneficial response to immunotherapy was larger for patients with high grade tumors (12 of 35; 34.3%) than those with low grade tumors (2 of 25, 8.0%) (difference, 26.3%; 95% confidence interval, 7.3%-45.3%). The odds of having a clinically beneficial response to immunotherapy was increased 5.35-fold (95% CI, 1.04-27.37) in patients with high-grade tumors. Among four patients with low-grade tumors and eight patients with high-grade tumors with available tumor mutational burden data, the mean tumor mutational burden was greater for patients with high-grade tumors (mean [standard deviation], 8.6 [5.4] mut/Mb; n = 8) than for patients with low grade tumors (mean [SD], 3.6 [1.1] mut/Mb; n = 4) (difference, 5.0 mut/Mb; 95% CI, −1.4 to 11.4 mut/Mb; Cohen d, 1.2).

“High tumor grade is not a guarantee but it possibly provides an easy biomarker and a good rationale to say that there’s a better chance the patient will respond to immune checkpoint inhibition,” said Dr. Mandal who is a head and neck cancer surgeon with the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Previous studies of HNSCC tumors that are refractory to traditional therapies, including surgery, chemotherapy, and radiation therapy, have demonstrated a clinically beneficial response to immune checkpoint inhibitors (ICIs). An association between increased tumor mutational burden and beneficial response to ICIs has been shown in other cancers.

Researchers hypothesized that tumor histological grade may be associated with responses to immune checkpoint blockade, and designed their study to examine the association between tumor grade and immunotherapy response in patients treated with ICIs for recurrent or metastatic mucosal HNSCC.

In a single-center retrospective cohort study, investigators reviewed the medical records of 60 adult patients (mean age, 64.6 years; 85% male) with a primary mucosal HNSCC tumor treated with an immune checkpoint inhibitor (pembrolizumab, nivolumab, ipilimumab, or durvalumab) treated between July 1, 2015, and Jan. 22, 2020. They stratified them into those with low grade tumors (well differentiated and moderately differentiated) and those with high grade tumors (poorly differentiated). A clinically beneficial immunotherapy response, defined as complete response or partial response was the primary outcome.

Thirty-eight patients in the study cohort were current or former smokers. The most common primary tumor sight was at the oropharynx. Outcomes among those with high-grade tumors were improved, compared with those with low-grade tumors, for median progression-free survival (5.9 months vs. 3.3 months), median overall survival (16.6 months vs. 15.0 months, and risk of death (hazard ratio, 0.94).

The study’s main limitation was its small sample size and small number of patients who had a clinically beneficial immunotherapy response.

Dr. Mandal had no conflicts of interest to disclose.

Findings from a cohort study highlight a potential role of tumor grade for predicting mucosal head and neck squamous cell carcinoma response to immunotherapy, researchers report in JAMA Otolaryngology–Head & Neck Surgery.

The analysis, which was among patients with either high-grade or low-grade recurrent or metastatic mucosal head and neck squamous cell carcinoma (HNSCC) tumors, revealed that tumor grade was independently associated with immunotherapy response.

“Generally, one would expect high-grade tumors to do worse because they are more aggressive,” said Rajarsi Mandal, MD, the study’s lead author. “But it’s thought that high-grade tumors have higher degrees of chromosomal instability with a lot more mutations generated throughout the genome of these tumors ... and we know that higher mutation rates correlate with higher responses to immunotherapy.”

Researchers found that the proportion of patients having a beneficial response to immunotherapy was larger for patients with high grade tumors (12 of 35; 34.3%) than those with low grade tumors (2 of 25, 8.0%) (difference, 26.3%; 95% confidence interval, 7.3%-45.3%). The odds of having a clinically beneficial response to immunotherapy was increased 5.35-fold (95% CI, 1.04-27.37) in patients with high-grade tumors. Among four patients with low-grade tumors and eight patients with high-grade tumors with available tumor mutational burden data, the mean tumor mutational burden was greater for patients with high-grade tumors (mean [standard deviation], 8.6 [5.4] mut/Mb; n = 8) than for patients with low grade tumors (mean [SD], 3.6 [1.1] mut/Mb; n = 4) (difference, 5.0 mut/Mb; 95% CI, −1.4 to 11.4 mut/Mb; Cohen d, 1.2).

“High tumor grade is not a guarantee but it possibly provides an easy biomarker and a good rationale to say that there’s a better chance the patient will respond to immune checkpoint inhibition,” said Dr. Mandal who is a head and neck cancer surgeon with the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Previous studies of HNSCC tumors that are refractory to traditional therapies, including surgery, chemotherapy, and radiation therapy, have demonstrated a clinically beneficial response to immune checkpoint inhibitors (ICIs). An association between increased tumor mutational burden and beneficial response to ICIs has been shown in other cancers.

Researchers hypothesized that tumor histological grade may be associated with responses to immune checkpoint blockade, and designed their study to examine the association between tumor grade and immunotherapy response in patients treated with ICIs for recurrent or metastatic mucosal HNSCC.

In a single-center retrospective cohort study, investigators reviewed the medical records of 60 adult patients (mean age, 64.6 years; 85% male) with a primary mucosal HNSCC tumor treated with an immune checkpoint inhibitor (pembrolizumab, nivolumab, ipilimumab, or durvalumab) treated between July 1, 2015, and Jan. 22, 2020. They stratified them into those with low grade tumors (well differentiated and moderately differentiated) and those with high grade tumors (poorly differentiated). A clinically beneficial immunotherapy response, defined as complete response or partial response was the primary outcome.

Thirty-eight patients in the study cohort were current or former smokers. The most common primary tumor sight was at the oropharynx. Outcomes among those with high-grade tumors were improved, compared with those with low-grade tumors, for median progression-free survival (5.9 months vs. 3.3 months), median overall survival (16.6 months vs. 15.0 months, and risk of death (hazard ratio, 0.94).

The study’s main limitation was its small sample size and small number of patients who had a clinically beneficial immunotherapy response.

Dr. Mandal had no conflicts of interest to disclose.

Findings from a cohort study highlight a potential role of tumor grade for predicting mucosal head and neck squamous cell carcinoma response to immunotherapy, researchers report in JAMA Otolaryngology–Head & Neck Surgery.

The analysis, which was among patients with either high-grade or low-grade recurrent or metastatic mucosal head and neck squamous cell carcinoma (HNSCC) tumors, revealed that tumor grade was independently associated with immunotherapy response.

“Generally, one would expect high-grade tumors to do worse because they are more aggressive,” said Rajarsi Mandal, MD, the study’s lead author. “But it’s thought that high-grade tumors have higher degrees of chromosomal instability with a lot more mutations generated throughout the genome of these tumors ... and we know that higher mutation rates correlate with higher responses to immunotherapy.”

Researchers found that the proportion of patients having a beneficial response to immunotherapy was larger for patients with high grade tumors (12 of 35; 34.3%) than those with low grade tumors (2 of 25, 8.0%) (difference, 26.3%; 95% confidence interval, 7.3%-45.3%). The odds of having a clinically beneficial response to immunotherapy was increased 5.35-fold (95% CI, 1.04-27.37) in patients with high-grade tumors. Among four patients with low-grade tumors and eight patients with high-grade tumors with available tumor mutational burden data, the mean tumor mutational burden was greater for patients with high-grade tumors (mean [standard deviation], 8.6 [5.4] mut/Mb; n = 8) than for patients with low grade tumors (mean [SD], 3.6 [1.1] mut/Mb; n = 4) (difference, 5.0 mut/Mb; 95% CI, −1.4 to 11.4 mut/Mb; Cohen d, 1.2).

“High tumor grade is not a guarantee but it possibly provides an easy biomarker and a good rationale to say that there’s a better chance the patient will respond to immune checkpoint inhibition,” said Dr. Mandal who is a head and neck cancer surgeon with the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Previous studies of HNSCC tumors that are refractory to traditional therapies, including surgery, chemotherapy, and radiation therapy, have demonstrated a clinically beneficial response to immune checkpoint inhibitors (ICIs). An association between increased tumor mutational burden and beneficial response to ICIs has been shown in other cancers.

Researchers hypothesized that tumor histological grade may be associated with responses to immune checkpoint blockade, and designed their study to examine the association between tumor grade and immunotherapy response in patients treated with ICIs for recurrent or metastatic mucosal HNSCC.

In a single-center retrospective cohort study, investigators reviewed the medical records of 60 adult patients (mean age, 64.6 years; 85% male) with a primary mucosal HNSCC tumor treated with an immune checkpoint inhibitor (pembrolizumab, nivolumab, ipilimumab, or durvalumab) treated between July 1, 2015, and Jan. 22, 2020. They stratified them into those with low grade tumors (well differentiated and moderately differentiated) and those with high grade tumors (poorly differentiated). A clinically beneficial immunotherapy response, defined as complete response or partial response was the primary outcome.

Thirty-eight patients in the study cohort were current or former smokers. The most common primary tumor sight was at the oropharynx. Outcomes among those with high-grade tumors were improved, compared with those with low-grade tumors, for median progression-free survival (5.9 months vs. 3.3 months), median overall survival (16.6 months vs. 15.0 months, and risk of death (hazard ratio, 0.94).

The study’s main limitation was its small sample size and small number of patients who had a clinically beneficial immunotherapy response.

Dr. Mandal had no conflicts of interest to disclose.

When asthma patients are having frequent clinical deteriorations, clinicians need to evaluate them for the presence and severity of bronchiectasis, according to the authors of a retrospective study in the Journal of Allergy and Clinical Immunology: In Practice. While bronchiectasis is known to worsen the clinical and functional outcomes in patients with asthma, data regarding the long-term effects of bronchiectasis on the clinical course of asthma have been limited, stated corresponding author Jung-Kyu Lee, MD, division of pulmonary and critical care medicine, Seoul (Republic of Korea) Metropolitan Government – Seoul National University.

Moderate to severe acute clinical deterioration risks were increased among the 251 patients (mean age 66.6 years, 77.2% men) with bronchiectasis out of 667 asthma patients included in the study. All studied patients underwent chest computed tomography and pulmonary function tests from 2013 to 2019 at two tertiary hospitals in Seoul. The primary outcome, annual incidence of moderate to severe acute exacerbations requiring additional treatment (systemic steroids, antibiotics, or both), was significantly higher in patients with bronchiectasis after a mean follow-up period of 3.96 years. Compared with patients who did not exhibit bronchiectasis, the annual rates of severe exacerbations (0.15 ± 0.43 vs. 0.08 ± 0.27; P = .010), moderate to severe (0.47 ± 0.79 vs. 0.34 ± 0.63; P = .018), and acute exacerbations during the follow-up period (49.8% vs. 39.4%; P = .009) were all significantly higher. There was no difference in the proportion of frequent exacerbators between the two groups, however. Severe acute exacerbations leading to hospitalizations, also, were more frequent in the group with bronchiectasis.
 

Risk factors explored

Significant factors conferring greater risk of severe and moderate to severe acute exacerbations in multivariable analysis included low body mass index, low baseline forced expiratory volume in 1 second (FEV₁), high use of inhaled corticosteroids, high medication possession, and high neutrophil/lymphocyte ratios. The existence of bronchiectasis remained an independent risk factor for severe and moderate to severe acute exacerbations despite adjustment for all other factors. While bronchiectasis score showed no association with annual rate of acute exacerbation, progression of bronchiectasis confirmed on follow-up CT was associated with increased risks of severe and moderate to severe acute exacerbation.

Included patients had a diagnosis of asthma confirmed by variable expiratory airflow limitation with pulmonary function tests (that is, positive bronchodilator response, positive bronchial provocation test, or excessive variation in lung function between visits). Past histories of tuberculosis and nontuberculous mycobacterial lung disease, lower absolute and predicted values of both baseline FEV₁ and forced vital capacity were more common among patients with bronchiectasis.

Dividing the study population into a group that had at least one moderate to severe acute exacerbation during the follow-up period and a group that did not, the researchers identified characteristics shared by exacerbators: a greater proportion were women, they had lower forced vital capacity and lung-diffusing capacity for carbon monoxide, higher blood FVC and blood neutrophil/lymphocyte ratio, and more medication use (inhaled corticosteroids, long-acting antimuscarinic agent, leukotriene-receptor antagonist, and methylxanthine), compared with the nonexacerbators. More bronchiectasis, more severe bronchiectasis (higher bronchiectasis score), and more progression of bronchiectasis were common among the exacerbators.

Higher acute exacerbation risks accompanied bronchiectasis, at 1.47-fold for moderate, 1.72-fold for severe, and 1.50-fold for moderate to severe exacerbations. Higher risk for severe and moderate to severe exacerbations was conferred by bronchiectasis progression, also.

The researchers pointed to contradictory effects of inhaled corticosteroid use, noting both corticosteroids’ essential role in controlling airway inflammation and hyperresponsiveness, exacerbations, and lung-function decline in asthma patients and that longer or greater inhaled corticosteroid use is associated with both clinical deterioration in asthma and bronchiectasis, and exacerbation history. For bronchiectasis, however, inhaled corticosteroid use offers no benefit while increasing susceptibility to infection and its risks through partial immunosuppression.

“Considering these contradictory effects of inhaled corticosteroid use, further research is needed regarding its risks and benefits in asthma patients with bronchiectasis, including differences in the benefit of inhaled corticosteroid use according to patient phenotype,” Dr. Kim and his colleagues concluded.
 

The role of corticosteroids

“One of the more important points discussed in this observational cohort study is the role of inhaled corticosteroid use in bronchiectasis,” said Mary Jo Farmer, MD, PhD, director of pulmonary hypertension services, Baystate Health, and assistant professor of medicine, University of Massachusetts – Baystate, both in Springfield, in an interview with this news organization. She cited a review finding no significant benefit versus placebo in spirometry, exacerbation rate, or sputum volume in the Cochrane Database of Systematic Reviews and another suggesting that quality of life was improved with inhaled corticosteroid use in individuals with blood eosinophils greater than 3%, compared with those not using inhaled corticosteroids or having lower eosinophil counts in the European Respiratory Journal. She cited also higher percentages (48% versus 23%) of adrenal insufficiency in bronchiectasis patients among those taking inhaled corticosteroids versus those not taking them.

Dr. Farmer added, “According to the 2018 Cochrane review of inhaled corticosteroid treatment for non–cystic fibrosis bronchiectasis, results from most randomized, placebo-controlled trials have been disappointing in terms of effects on most endpoints such as pulmonary function and exacerbation frequency. As such, the European Respiratory Society guidelines for the management of adult bronchiectasis advise against prescribing inhaled corticosteroids to patients with bronchiectasis, unless otherwise indicated by either an asthma or chronic obstructive pulmonary disease diagnosis. Also, inhaled corticosteroid treatment in asthma and COPD is associated with common side effects such as oral candidiasis, dysphonia and, in some cases, systemic corticosteroid effects. The rate of adverse events from inhaled corticosteroid treatment of bronchiectasis, however, is largely unknown.Dr. Lee and Dr. Farmer reported no relevant financial relationships. The study was independently supported.

When asthma patients are having frequent clinical deteriorations, clinicians need to evaluate them for the presence and severity of bronchiectasis, according to the authors of a retrospective study in the Journal of Allergy and Clinical Immunology: In Practice. While bronchiectasis is known to worsen the clinical and functional outcomes in patients with asthma, data regarding the long-term effects of bronchiectasis on the clinical course of asthma have been limited, stated corresponding author Jung-Kyu Lee, MD, division of pulmonary and critical care medicine, Seoul (Republic of Korea) Metropolitan Government – Seoul National University.

Moderate to severe acute clinical deterioration risks were increased among the 251 patients (mean age 66.6 years, 77.2% men) with bronchiectasis out of 667 asthma patients included in the study. All studied patients underwent chest computed tomography and pulmonary function tests from 2013 to 2019 at two tertiary hospitals in Seoul. The primary outcome, annual incidence of moderate to severe acute exacerbations requiring additional treatment (systemic steroids, antibiotics, or both), was significantly higher in patients with bronchiectasis after a mean follow-up period of 3.96 years. Compared with patients who did not exhibit bronchiectasis, the annual rates of severe exacerbations (0.15 ± 0.43 vs. 0.08 ± 0.27; P = .010), moderate to severe (0.47 ± 0.79 vs. 0.34 ± 0.63; P = .018), and acute exacerbations during the follow-up period (49.8% vs. 39.4%; P = .009) were all significantly higher. There was no difference in the proportion of frequent exacerbators between the two groups, however. Severe acute exacerbations leading to hospitalizations, also, were more frequent in the group with bronchiectasis.
 

Risk factors explored

Significant factors conferring greater risk of severe and moderate to severe acute exacerbations in multivariable analysis included low body mass index, low baseline forced expiratory volume in 1 second (FEV₁), high use of inhaled corticosteroids, high medication possession, and high neutrophil/lymphocyte ratios. The existence of bronchiectasis remained an independent risk factor for severe and moderate to severe acute exacerbations despite adjustment for all other factors. While bronchiectasis score showed no association with annual rate of acute exacerbation, progression of bronchiectasis confirmed on follow-up CT was associated with increased risks of severe and moderate to severe acute exacerbation.

Included patients had a diagnosis of asthma confirmed by variable expiratory airflow limitation with pulmonary function tests (that is, positive bronchodilator response, positive bronchial provocation test, or excessive variation in lung function between visits). Past histories of tuberculosis and nontuberculous mycobacterial lung disease, lower absolute and predicted values of both baseline FEV₁ and forced vital capacity were more common among patients with bronchiectasis.

Dividing the study population into a group that had at least one moderate to severe acute exacerbation during the follow-up period and a group that did not, the researchers identified characteristics shared by exacerbators: a greater proportion were women, they had lower forced vital capacity and lung-diffusing capacity for carbon monoxide, higher blood FVC and blood neutrophil/lymphocyte ratio, and more medication use (inhaled corticosteroids, long-acting antimuscarinic agent, leukotriene-receptor antagonist, and methylxanthine), compared with the nonexacerbators. More bronchiectasis, more severe bronchiectasis (higher bronchiectasis score), and more progression of bronchiectasis were common among the exacerbators.

Higher acute exacerbation risks accompanied bronchiectasis, at 1.47-fold for moderate, 1.72-fold for severe, and 1.50-fold for moderate to severe exacerbations. Higher risk for severe and moderate to severe exacerbations was conferred by bronchiectasis progression, also.

The researchers pointed to contradictory effects of inhaled corticosteroid use, noting both corticosteroids’ essential role in controlling airway inflammation and hyperresponsiveness, exacerbations, and lung-function decline in asthma patients and that longer or greater inhaled corticosteroid use is associated with both clinical deterioration in asthma and bronchiectasis, and exacerbation history. For bronchiectasis, however, inhaled corticosteroid use offers no benefit while increasing susceptibility to infection and its risks through partial immunosuppression.

“Considering these contradictory effects of inhaled corticosteroid use, further research is needed regarding its risks and benefits in asthma patients with bronchiectasis, including differences in the benefit of inhaled corticosteroid use according to patient phenotype,” Dr. Kim and his colleagues concluded.
 

The role of corticosteroids

“One of the more important points discussed in this observational cohort study is the role of inhaled corticosteroid use in bronchiectasis,” said Mary Jo Farmer, MD, PhD, director of pulmonary hypertension services, Baystate Health, and assistant professor of medicine, University of Massachusetts – Baystate, both in Springfield, in an interview with this news organization. She cited a review finding no significant benefit versus placebo in spirometry, exacerbation rate, or sputum volume in the Cochrane Database of Systematic Reviews and another suggesting that quality of life was improved with inhaled corticosteroid use in individuals with blood eosinophils greater than 3%, compared with those not using inhaled corticosteroids or having lower eosinophil counts in the European Respiratory Journal. She cited also higher percentages (48% versus 23%) of adrenal insufficiency in bronchiectasis patients among those taking inhaled corticosteroids versus those not taking them.

Dr. Farmer added, “According to the 2018 Cochrane review of inhaled corticosteroid treatment for non–cystic fibrosis bronchiectasis, results from most randomized, placebo-controlled trials have been disappointing in terms of effects on most endpoints such as pulmonary function and exacerbation frequency. As such, the European Respiratory Society guidelines for the management of adult bronchiectasis advise against prescribing inhaled corticosteroids to patients with bronchiectasis, unless otherwise indicated by either an asthma or chronic obstructive pulmonary disease diagnosis. Also, inhaled corticosteroid treatment in asthma and COPD is associated with common side effects such as oral candidiasis, dysphonia and, in some cases, systemic corticosteroid effects. The rate of adverse events from inhaled corticosteroid treatment of bronchiectasis, however, is largely unknown.Dr. Lee and Dr. Farmer reported no relevant financial relationships. The study was independently supported.

When asthma patients are having frequent clinical deteriorations, clinicians need to evaluate them for the presence and severity of bronchiectasis, according to the authors of a retrospective study in the Journal of Allergy and Clinical Immunology: In Practice. While bronchiectasis is known to worsen the clinical and functional outcomes in patients with asthma, data regarding the long-term effects of bronchiectasis on the clinical course of asthma have been limited, stated corresponding author Jung-Kyu Lee, MD, division of pulmonary and critical care medicine, Seoul (Republic of Korea) Metropolitan Government – Seoul National University.

Moderate to severe acute clinical deterioration risks were increased among the 251 patients (mean age 66.6 years, 77.2% men) with bronchiectasis out of 667 asthma patients included in the study. All studied patients underwent chest computed tomography and pulmonary function tests from 2013 to 2019 at two tertiary hospitals in Seoul. The primary outcome, annual incidence of moderate to severe acute exacerbations requiring additional treatment (systemic steroids, antibiotics, or both), was significantly higher in patients with bronchiectasis after a mean follow-up period of 3.96 years. Compared with patients who did not exhibit bronchiectasis, the annual rates of severe exacerbations (0.15 ± 0.43 vs. 0.08 ± 0.27; P = .010), moderate to severe (0.47 ± 0.79 vs. 0.34 ± 0.63; P = .018), and acute exacerbations during the follow-up period (49.8% vs. 39.4%; P = .009) were all significantly higher. There was no difference in the proportion of frequent exacerbators between the two groups, however. Severe acute exacerbations leading to hospitalizations, also, were more frequent in the group with bronchiectasis.
 

Risk factors explored

Significant factors conferring greater risk of severe and moderate to severe acute exacerbations in multivariable analysis included low body mass index, low baseline forced expiratory volume in 1 second (FEV₁), high use of inhaled corticosteroids, high medication possession, and high neutrophil/lymphocyte ratios. The existence of bronchiectasis remained an independent risk factor for severe and moderate to severe acute exacerbations despite adjustment for all other factors. While bronchiectasis score showed no association with annual rate of acute exacerbation, progression of bronchiectasis confirmed on follow-up CT was associated with increased risks of severe and moderate to severe acute exacerbation.

Included patients had a diagnosis of asthma confirmed by variable expiratory airflow limitation with pulmonary function tests (that is, positive bronchodilator response, positive bronchial provocation test, or excessive variation in lung function between visits). Past histories of tuberculosis and nontuberculous mycobacterial lung disease, lower absolute and predicted values of both baseline FEV₁ and forced vital capacity were more common among patients with bronchiectasis.

Dividing the study population into a group that had at least one moderate to severe acute exacerbation during the follow-up period and a group that did not, the researchers identified characteristics shared by exacerbators: a greater proportion were women, they had lower forced vital capacity and lung-diffusing capacity for carbon monoxide, higher blood FVC and blood neutrophil/lymphocyte ratio, and more medication use (inhaled corticosteroids, long-acting antimuscarinic agent, leukotriene-receptor antagonist, and methylxanthine), compared with the nonexacerbators. More bronchiectasis, more severe bronchiectasis (higher bronchiectasis score), and more progression of bronchiectasis were common among the exacerbators.

Higher acute exacerbation risks accompanied bronchiectasis, at 1.47-fold for moderate, 1.72-fold for severe, and 1.50-fold for moderate to severe exacerbations. Higher risk for severe and moderate to severe exacerbations was conferred by bronchiectasis progression, also.

The researchers pointed to contradictory effects of inhaled corticosteroid use, noting both corticosteroids’ essential role in controlling airway inflammation and hyperresponsiveness, exacerbations, and lung-function decline in asthma patients and that longer or greater inhaled corticosteroid use is associated with both clinical deterioration in asthma and bronchiectasis, and exacerbation history. For bronchiectasis, however, inhaled corticosteroid use offers no benefit while increasing susceptibility to infection and its risks through partial immunosuppression.

“Considering these contradictory effects of inhaled corticosteroid use, further research is needed regarding its risks and benefits in asthma patients with bronchiectasis, including differences in the benefit of inhaled corticosteroid use according to patient phenotype,” Dr. Kim and his colleagues concluded.
 

The role of corticosteroids

“One of the more important points discussed in this observational cohort study is the role of inhaled corticosteroid use in bronchiectasis,” said Mary Jo Farmer, MD, PhD, director of pulmonary hypertension services, Baystate Health, and assistant professor of medicine, University of Massachusetts – Baystate, both in Springfield, in an interview with this news organization. She cited a review finding no significant benefit versus placebo in spirometry, exacerbation rate, or sputum volume in the Cochrane Database of Systematic Reviews and another suggesting that quality of life was improved with inhaled corticosteroid use in individuals with blood eosinophils greater than 3%, compared with those not using inhaled corticosteroids or having lower eosinophil counts in the European Respiratory Journal. She cited also higher percentages (48% versus 23%) of adrenal insufficiency in bronchiectasis patients among those taking inhaled corticosteroids versus those not taking them.

Dr. Farmer added, “According to the 2018 Cochrane review of inhaled corticosteroid treatment for non–cystic fibrosis bronchiectasis, results from most randomized, placebo-controlled trials have been disappointing in terms of effects on most endpoints such as pulmonary function and exacerbation frequency. As such, the European Respiratory Society guidelines for the management of adult bronchiectasis advise against prescribing inhaled corticosteroids to patients with bronchiectasis, unless otherwise indicated by either an asthma or chronic obstructive pulmonary disease diagnosis. Also, inhaled corticosteroid treatment in asthma and COPD is associated with common side effects such as oral candidiasis, dysphonia and, in some cases, systemic corticosteroid effects. The rate of adverse events from inhaled corticosteroid treatment of bronchiectasis, however, is largely unknown.Dr. Lee and Dr. Farmer reported no relevant financial relationships. The study was independently supported.

Hormone receptor positive (HR+) basal tumors are biologically analogous to triple negative breast cancer (TNBC), independent of race. That finding, suggested by transcriptomic analyses of a racially diverse cohort that identified racial disparities in the proportion of HR-positive basal tumors, underscores a need for diverse racial representation in clinical trials, researchers recently reported at the annual meeting of the American Society of Clinical Oncology.

The leading cause of cancer-associated death among Black women is breast cancer, and compared with White women, Black women are 41% more likely to die from breast cancer, said Sonya A. Reid, MD, MPH, a medical oncologist with the Vanderbilt-Ingram Cancer Center, Nashville, Tenn., and the study author.

Few studies, Dr. Reid said, have evaluated if tumor biology differences contribute to the racial outcome disparity. Hormone receptor-positive tumors classified as basal-type with Blueprint genomic analysis (HR+/Basal) are overrepresented among Black women. These tumors are thought to be similar to triple negative breast cancer tumors (TNBC) which are more aggressive and tend to have worse outcomes.

TNBC, Dr. Reid said, is associated with low ACKR1 expression, which encodes the Duffy antigen and correlates with worse breast cancer outcomes. Given the overrepresentation and worse outcomes among Black women with HR-positive basal tumors, Dr. Reid and colleagues compared differentially expressed genes (DEGs) by race and subtype.

Their analysis of data from 2,657 women with stage 1, 2, and 3 breast cancer, showed that among 455 Black women, 315 had luminal (HR-positive luminal) and 140 had basal tumors (66 HR-positive basal and 74 HR-negative basal). Among White women included as a reference group (n = 2,202), tumors were were HR-positive luminal in 1,825 and HR-positive basal or HR-negative basal in 158 and 219, respectively. The proportion of Black women with HR-positive basal tumors was significantly higher, compared with White women (15% versus 7%; P <0.001) as was the proportion of Black women with HR-negative basal tumors, compared with White women (16% versus 10%; P <0.001).

Women included in the study were participants in the ongoing BEST study (5R01CA204819) at Vanderbilt University Medical Center, Nashvlile, Tenn., or FLEX study (NCT03053193). In a multidimensional scaling analysis, HR-positive basal tumors clustered with TNBC rather than with HR-positive luminal tumors. While a differential gene expression analysis comparing HR-positive basal with HR-positive luminal tumors resulted in over 700 differently expressed genes in Black women, no such genes were identified when comparing HR-positive basal tumors with TNBC. ACKR1 expression in HR-positive basal tumors was comparable to TNBC in Black women (P = 0.81) and White women (P = 0.46). In contrast, HR-positive basal tumors had significantly lower ACKR1 expression than HR-positive luminal tumors in Black (P < 0.01) and White women (P < 0.01).

The findings highlight the importance of further genomic classification for patients with HR-positive tumors, Dr. Reid said.

“Molecular subtype classification is not standard of care for patients with localized breast cancer. However, the current analysis suggests that genomic classification could have important clinical implications. Women with HR-positive basal tumors should not be treated uniformly with HR-poisitive luminal tumors. Our data suggest that HR-positive basal tumors are transcriptomically similar to TNBC tumors and should potentially be treated similar to TNBC,” she said.

There are several genomic tests that are widely available clinically to guide treatment decisions and are covered by insurance, Dr. Reid said. Prior studies have shown racial disparity in the omission of genomic tests to guide treatment decisions, however. “Increasing access [to] and awareness of genomic testing will improve guideline-adherent care for all patients. We must intentionally recruit minority patients into clinical trials, knowing that Black women are more likely to die of their breast cancer,” she said.

A further impediment lies in the fact that while most minority patients receive their care in the community, most clinical trials are offered at large academic centers, Dr. Reid said. Future trials, she urged, should include a predetermined percentage of racial/ethnic groups in the clinical trial design to reflect the breast cancer population.

Limitations of the study included that race was self-reported. She noted further that the data for survival are not yet mature. She added, “We will also be evaluating the association of different systemic treatment options across the different molecular subtypes.”

Dr. Reid reported no relevant disclosures.

Hormone receptor positive (HR+) basal tumors are biologically analogous to triple negative breast cancer (TNBC), independent of race. That finding, suggested by transcriptomic analyses of a racially diverse cohort that identified racial disparities in the proportion of HR-positive basal tumors, underscores a need for diverse racial representation in clinical trials, researchers recently reported at the annual meeting of the American Society of Clinical Oncology.

The leading cause of cancer-associated death among Black women is breast cancer, and compared with White women, Black women are 41% more likely to die from breast cancer, said Sonya A. Reid, MD, MPH, a medical oncologist with the Vanderbilt-Ingram Cancer Center, Nashville, Tenn., and the study author.

Few studies, Dr. Reid said, have evaluated if tumor biology differences contribute to the racial outcome disparity. Hormone receptor-positive tumors classified as basal-type with Blueprint genomic analysis (HR+/Basal) are overrepresented among Black women. These tumors are thought to be similar to triple negative breast cancer tumors (TNBC) which are more aggressive and tend to have worse outcomes.

TNBC, Dr. Reid said, is associated with low ACKR1 expression, which encodes the Duffy antigen and correlates with worse breast cancer outcomes. Given the overrepresentation and worse outcomes among Black women with HR-positive basal tumors, Dr. Reid and colleagues compared differentially expressed genes (DEGs) by race and subtype.

Their analysis of data from 2,657 women with stage 1, 2, and 3 breast cancer, showed that among 455 Black women, 315 had luminal (HR-positive luminal) and 140 had basal tumors (66 HR-positive basal and 74 HR-negative basal). Among White women included as a reference group (n = 2,202), tumors were were HR-positive luminal in 1,825 and HR-positive basal or HR-negative basal in 158 and 219, respectively. The proportion of Black women with HR-positive basal tumors was significantly higher, compared with White women (15% versus 7%; P <0.001) as was the proportion of Black women with HR-negative basal tumors, compared with White women (16% versus 10%; P <0.001).

Women included in the study were participants in the ongoing BEST study (5R01CA204819) at Vanderbilt University Medical Center, Nashvlile, Tenn., or FLEX study (NCT03053193). In a multidimensional scaling analysis, HR-positive basal tumors clustered with TNBC rather than with HR-positive luminal tumors. While a differential gene expression analysis comparing HR-positive basal with HR-positive luminal tumors resulted in over 700 differently expressed genes in Black women, no such genes were identified when comparing HR-positive basal tumors with TNBC. ACKR1 expression in HR-positive basal tumors was comparable to TNBC in Black women (P = 0.81) and White women (P = 0.46). In contrast, HR-positive basal tumors had significantly lower ACKR1 expression than HR-positive luminal tumors in Black (P < 0.01) and White women (P < 0.01).

The findings highlight the importance of further genomic classification for patients with HR-positive tumors, Dr. Reid said.

“Molecular subtype classification is not standard of care for patients with localized breast cancer. However, the current analysis suggests that genomic classification could have important clinical implications. Women with HR-positive basal tumors should not be treated uniformly with HR-poisitive luminal tumors. Our data suggest that HR-positive basal tumors are transcriptomically similar to TNBC tumors and should potentially be treated similar to TNBC,” she said.

There are several genomic tests that are widely available clinically to guide treatment decisions and are covered by insurance, Dr. Reid said. Prior studies have shown racial disparity in the omission of genomic tests to guide treatment decisions, however. “Increasing access [to] and awareness of genomic testing will improve guideline-adherent care for all patients. We must intentionally recruit minority patients into clinical trials, knowing that Black women are more likely to die of their breast cancer,” she said.

A further impediment lies in the fact that while most minority patients receive their care in the community, most clinical trials are offered at large academic centers, Dr. Reid said. Future trials, she urged, should include a predetermined percentage of racial/ethnic groups in the clinical trial design to reflect the breast cancer population.

Limitations of the study included that race was self-reported. She noted further that the data for survival are not yet mature. She added, “We will also be evaluating the association of different systemic treatment options across the different molecular subtypes.”

Dr. Reid reported no relevant disclosures.

Hormone receptor positive (HR+) basal tumors are biologically analogous to triple negative breast cancer (TNBC), independent of race. That finding, suggested by transcriptomic analyses of a racially diverse cohort that identified racial disparities in the proportion of HR-positive basal tumors, underscores a need for diverse racial representation in clinical trials, researchers recently reported at the annual meeting of the American Society of Clinical Oncology.

The leading cause of cancer-associated death among Black women is breast cancer, and compared with White women, Black women are 41% more likely to die from breast cancer, said Sonya A. Reid, MD, MPH, a medical oncologist with the Vanderbilt-Ingram Cancer Center, Nashville, Tenn., and the study author.

Few studies, Dr. Reid said, have evaluated if tumor biology differences contribute to the racial outcome disparity. Hormone receptor-positive tumors classified as basal-type with Blueprint genomic analysis (HR+/Basal) are overrepresented among Black women. These tumors are thought to be similar to triple negative breast cancer tumors (TNBC) which are more aggressive and tend to have worse outcomes.

TNBC, Dr. Reid said, is associated with low ACKR1 expression, which encodes the Duffy antigen and correlates with worse breast cancer outcomes. Given the overrepresentation and worse outcomes among Black women with HR-positive basal tumors, Dr. Reid and colleagues compared differentially expressed genes (DEGs) by race and subtype.

Their analysis of data from 2,657 women with stage 1, 2, and 3 breast cancer, showed that among 455 Black women, 315 had luminal (HR-positive luminal) and 140 had basal tumors (66 HR-positive basal and 74 HR-negative basal). Among White women included as a reference group (n = 2,202), tumors were were HR-positive luminal in 1,825 and HR-positive basal or HR-negative basal in 158 and 219, respectively. The proportion of Black women with HR-positive basal tumors was significantly higher, compared with White women (15% versus 7%; P <0.001) as was the proportion of Black women with HR-negative basal tumors, compared with White women (16% versus 10%; P <0.001).

Women included in the study were participants in the ongoing BEST study (5R01CA204819) at Vanderbilt University Medical Center, Nashvlile, Tenn., or FLEX study (NCT03053193). In a multidimensional scaling analysis, HR-positive basal tumors clustered with TNBC rather than with HR-positive luminal tumors. While a differential gene expression analysis comparing HR-positive basal with HR-positive luminal tumors resulted in over 700 differently expressed genes in Black women, no such genes were identified when comparing HR-positive basal tumors with TNBC. ACKR1 expression in HR-positive basal tumors was comparable to TNBC in Black women (P = 0.81) and White women (P = 0.46). In contrast, HR-positive basal tumors had significantly lower ACKR1 expression than HR-positive luminal tumors in Black (P < 0.01) and White women (P < 0.01).

The findings highlight the importance of further genomic classification for patients with HR-positive tumors, Dr. Reid said.

“Molecular subtype classification is not standard of care for patients with localized breast cancer. However, the current analysis suggests that genomic classification could have important clinical implications. Women with HR-positive basal tumors should not be treated uniformly with HR-poisitive luminal tumors. Our data suggest that HR-positive basal tumors are transcriptomically similar to TNBC tumors and should potentially be treated similar to TNBC,” she said.

There are several genomic tests that are widely available clinically to guide treatment decisions and are covered by insurance, Dr. Reid said. Prior studies have shown racial disparity in the omission of genomic tests to guide treatment decisions, however. “Increasing access [to] and awareness of genomic testing will improve guideline-adherent care for all patients. We must intentionally recruit minority patients into clinical trials, knowing that Black women are more likely to die of their breast cancer,” she said.

A further impediment lies in the fact that while most minority patients receive their care in the community, most clinical trials are offered at large academic centers, Dr. Reid said. Future trials, she urged, should include a predetermined percentage of racial/ethnic groups in the clinical trial design to reflect the breast cancer population.

Limitations of the study included that race was self-reported. She noted further that the data for survival are not yet mature. She added, “We will also be evaluating the association of different systemic treatment options across the different molecular subtypes.”

Dr. Reid reported no relevant disclosures.

A study of elderly patients with HER2-positive/HR-negative metastatic breast cancer finds a significantly shorter median overall survival in actual clinical practice than younger counterparts.

After 46 months of treatment, the survival rate was only 25%, according to a study presented in June at the annual meeting of the American Society of Clinical Oncology. The finding suggests that older age is an important prognostic factor for breast cancer survival, said study author Zhonghui Jenny Ou, a doctoral candidate at the Massachusetts College of Pharmacy and Health Sciences in Boston.

For comparison, Ms. Ou cited the CLEOPATRA trial which showed a median overall survival of 57.1 months for patients who were treated with pertuzumab, docetaxel and trastuzumab versus 40.8 months for placebo with docetaxel plus trastuzumab.

The Ou study is based on an analysis of data between 2012 and 2016 from the SEER-Medicare database. The final analysis included 73 women (average age 75 years at diagnosis) with early-stage HER2-positive/HR-negative metastatic breast cancer. Fifty-six women were treated with trastuzumab with pertuzumab and chemotherapy as first-line treatment, and 17 were treated with chemotherapy only. The longest length of treatment with trastuzumab was over 44 months. And, the median follow-up for overall survival was 13 months (95% confidence interval, 12.7-18.7).

Between 2012 and 2016, five patients died from other causes, including lung cancer, cerebrovascular diseases, aortic aneurysm and dissection, pneumonia and influenza, and heart disease.

“While there are many clinical trials about HER2-positive metastatic breast cancer, these trials were all performed in younger and relatively healthier patients. Few studies included elderly patients 65 years or older,” Ms. Ou said.

According to the American Cancer Society, 31% of all newly diagnosed breast cancer cases are in women who are 70 years old or older, yet 47% of all breast cancer deaths each year are in women in this age group.

Undertreatment and lower treatment intensity have been cited by other studies as possible contributing factors to lower overall survival rates, but breast cancer in elderly women is a complex and understudied subject. Why the mortality rates for elderly women are disproportionately higher than those of younger women is attributable to a number of reasons, write the authors of one of the most recent studies on the subject.

“It is well established that receipt of adjuvant chemotherapy, trastuzumab, and hormonal therapy reduces risk of recurrence and death across all age groups, yet multiple studies document suboptimal systemic treatment and adherence for older patients, including omission of efficacious treatments, receipt of lower intensity and/or nonguideline treatment, or poor adherence to hormonal therapy,” Freedman et al. wrote in the May 15, 2018, issue of the journal Cancer.

While the Ou study sample size was small, the study’s real-world analysis is telling, Ms. Ou said.

“The major limitation of this study is that it has – after applying all the eligibility criteria to the 170,516 breast cancer patients from the SEER-Medicare database between 2012 and 2016 – a study population of just 73 patients. The number is sufficient to do survival analysis,” she said.

A study of elderly patients with HER2-positive/HR-negative metastatic breast cancer finds a significantly shorter median overall survival in actual clinical practice than younger counterparts.

After 46 months of treatment, the survival rate was only 25%, according to a study presented in June at the annual meeting of the American Society of Clinical Oncology. The finding suggests that older age is an important prognostic factor for breast cancer survival, said study author Zhonghui Jenny Ou, a doctoral candidate at the Massachusetts College of Pharmacy and Health Sciences in Boston.

For comparison, Ms. Ou cited the CLEOPATRA trial which showed a median overall survival of 57.1 months for patients who were treated with pertuzumab, docetaxel and trastuzumab versus 40.8 months for placebo with docetaxel plus trastuzumab.

The Ou study is based on an analysis of data between 2012 and 2016 from the SEER-Medicare database. The final analysis included 73 women (average age 75 years at diagnosis) with early-stage HER2-positive/HR-negative metastatic breast cancer. Fifty-six women were treated with trastuzumab with pertuzumab and chemotherapy as first-line treatment, and 17 were treated with chemotherapy only. The longest length of treatment with trastuzumab was over 44 months. And, the median follow-up for overall survival was 13 months (95% confidence interval, 12.7-18.7).

Between 2012 and 2016, five patients died from other causes, including lung cancer, cerebrovascular diseases, aortic aneurysm and dissection, pneumonia and influenza, and heart disease.

“While there are many clinical trials about HER2-positive metastatic breast cancer, these trials were all performed in younger and relatively healthier patients. Few studies included elderly patients 65 years or older,” Ms. Ou said.

According to the American Cancer Society, 31% of all newly diagnosed breast cancer cases are in women who are 70 years old or older, yet 47% of all breast cancer deaths each year are in women in this age group.

Undertreatment and lower treatment intensity have been cited by other studies as possible contributing factors to lower overall survival rates, but breast cancer in elderly women is a complex and understudied subject. Why the mortality rates for elderly women are disproportionately higher than those of younger women is attributable to a number of reasons, write the authors of one of the most recent studies on the subject.

“It is well established that receipt of adjuvant chemotherapy, trastuzumab, and hormonal therapy reduces risk of recurrence and death across all age groups, yet multiple studies document suboptimal systemic treatment and adherence for older patients, including omission of efficacious treatments, receipt of lower intensity and/or nonguideline treatment, or poor adherence to hormonal therapy,” Freedman et al. wrote in the May 15, 2018, issue of the journal Cancer.

While the Ou study sample size was small, the study’s real-world analysis is telling, Ms. Ou said.

“The major limitation of this study is that it has – after applying all the eligibility criteria to the 170,516 breast cancer patients from the SEER-Medicare database between 2012 and 2016 – a study population of just 73 patients. The number is sufficient to do survival analysis,” she said.

A study of elderly patients with HER2-positive/HR-negative metastatic breast cancer finds a significantly shorter median overall survival in actual clinical practice than younger counterparts.

After 46 months of treatment, the survival rate was only 25%, according to a study presented in June at the annual meeting of the American Society of Clinical Oncology. The finding suggests that older age is an important prognostic factor for breast cancer survival, said study author Zhonghui Jenny Ou, a doctoral candidate at the Massachusetts College of Pharmacy and Health Sciences in Boston.

For comparison, Ms. Ou cited the CLEOPATRA trial which showed a median overall survival of 57.1 months for patients who were treated with pertuzumab, docetaxel and trastuzumab versus 40.8 months for placebo with docetaxel plus trastuzumab.

The Ou study is based on an analysis of data between 2012 and 2016 from the SEER-Medicare database. The final analysis included 73 women (average age 75 years at diagnosis) with early-stage HER2-positive/HR-negative metastatic breast cancer. Fifty-six women were treated with trastuzumab with pertuzumab and chemotherapy as first-line treatment, and 17 were treated with chemotherapy only. The longest length of treatment with trastuzumab was over 44 months. And, the median follow-up for overall survival was 13 months (95% confidence interval, 12.7-18.7).

Between 2012 and 2016, five patients died from other causes, including lung cancer, cerebrovascular diseases, aortic aneurysm and dissection, pneumonia and influenza, and heart disease.

“While there are many clinical trials about HER2-positive metastatic breast cancer, these trials were all performed in younger and relatively healthier patients. Few studies included elderly patients 65 years or older,” Ms. Ou said.

According to the American Cancer Society, 31% of all newly diagnosed breast cancer cases are in women who are 70 years old or older, yet 47% of all breast cancer deaths each year are in women in this age group.

Undertreatment and lower treatment intensity have been cited by other studies as possible contributing factors to lower overall survival rates, but breast cancer in elderly women is a complex and understudied subject. Why the mortality rates for elderly women are disproportionately higher than those of younger women is attributable to a number of reasons, write the authors of one of the most recent studies on the subject.

“It is well established that receipt of adjuvant chemotherapy, trastuzumab, and hormonal therapy reduces risk of recurrence and death across all age groups, yet multiple studies document suboptimal systemic treatment and adherence for older patients, including omission of efficacious treatments, receipt of lower intensity and/or nonguideline treatment, or poor adherence to hormonal therapy,” Freedman et al. wrote in the May 15, 2018, issue of the journal Cancer.

While the Ou study sample size was small, the study’s real-world analysis is telling, Ms. Ou said.

“The major limitation of this study is that it has – after applying all the eligibility criteria to the 170,516 breast cancer patients from the SEER-Medicare database between 2012 and 2016 – a study population of just 73 patients. The number is sufficient to do survival analysis,” she said.

Eight-year follow-up of the ASTRRA trial confirmed and extended support for adding 2 years of ovarian function suppression with goserelin to tamoxifen, compared with tamoxifen alone.

“Adding ovarian suppression to tamoxifen should be considered for this population of women,” said senior author Hee Jeong Kim, MD, a breast cancer surgeon with the Asan Medical Center, Seoul, South Korea. Dr. Kim presented the data earlier this month at the annual meeting of the American Society of Clinical Oncology.

The median disease-free survival rate of 85.4% for tamoxifen plus ovarian function suppression versus 80.2% for tamoxifen alone (HR, 0.67; 95% confidence interval, 0.514-0.869; P = .0027) was consistent with recent findings from SOFT (Suppression of Ovarian Function Trial), which also showed a clear survival benefit in breast cancer events with the addition of ovarian function suppression to tamoxifen for women who remain premenopausal after chemotherapy. SOFT trial analyses of disease-free survival at 5 and 8 years demonstrated hazard ratios of 0.82 and 0.76 respectively.

Dr. Kim’s study is a post-trial follow-up of the ASTRRA trial, or the Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy, which randomly assigned 1,298 patients with breast cancer in a one-to-one ratio to receive tamoxifen only (n = 647) or tamoxifen plus ovarian function suppression (n = 635). The primary endpoint was disease-free survival and the secondary endpoint was overall survival.

Earlier ASTRRA analysis at 5-year follow-up had shown disease-free survival rates of 89.9% for tamoxifen plus ovarian function suppression versus 87.2% for tamoxifen alone in women with hormone-sensitive breast cancer who remained premenopausal or had premenopausal status restored after chemotherapy. Overall survival, a secondary endpoint, also favored adding ovarian function suppression (HR, 0.31; 95% CI, 0.10-0.94; P = .029). The absolute difference for disease-free survival adding ovarian function suppression at the later median follow-up of 106.4 months was 5.2%. The difference at 5 years had been 2.7%, Dr. Kim pointed out. Also, these findings were calculated from time of enrollment. When calculated from time of randomization, the disease-free survival rates were 84.1% and 78.1%, respectively, for tamoxifen plus ovarian function suppression and tamoxifen alone, with a 6.0% absolute difference (HR, 0.67; 95% CI, 0.516-0.872); P = .0025).

The benefit of adding ovarian function suppression to tamoxifen for the secondary endpoint of overall survival at 8 years (96.5% versus 95.3%) did not achieve statistical significance (HR, 0.78; 95% CI, 0.486-1.253); P = .3). “Although it’s not statistically significant, there are absolute differences between the two groups favoring tamoxifen plus ovarian function suppression,” Dr. Kim said in an interview. She pointed out also that for distant metastasis-free survival the hazard ratio was 0.71, significantly favoring tamoxifen plus ovarian function suppression. “More than 95% were still surviving at 8 years with tamoxifen plus ovarian function suppression. So, we need more events to fully evaluate the overall survival benefit.”

A study limitation, Dr. Kim acknowledged in the interview, is that safety and adverse event data were not collected. “As ovarian function suppression has been widely used in clinical practice for decades, and the side effects of its relatively short-term use were considered to be well-understood in previous studies, we focused on the oncologic efficacy of ovarian function suppression in this study,” she said.

Eight-year follow-up of the ASTRRA trial confirmed and extended support for adding 2 years of ovarian function suppression with goserelin to tamoxifen, compared with tamoxifen alone.

“Adding ovarian suppression to tamoxifen should be considered for this population of women,” said senior author Hee Jeong Kim, MD, a breast cancer surgeon with the Asan Medical Center, Seoul, South Korea. Dr. Kim presented the data earlier this month at the annual meeting of the American Society of Clinical Oncology.

The median disease-free survival rate of 85.4% for tamoxifen plus ovarian function suppression versus 80.2% for tamoxifen alone (HR, 0.67; 95% confidence interval, 0.514-0.869; P = .0027) was consistent with recent findings from SOFT (Suppression of Ovarian Function Trial), which also showed a clear survival benefit in breast cancer events with the addition of ovarian function suppression to tamoxifen for women who remain premenopausal after chemotherapy. SOFT trial analyses of disease-free survival at 5 and 8 years demonstrated hazard ratios of 0.82 and 0.76 respectively.

Dr. Kim’s study is a post-trial follow-up of the ASTRRA trial, or the Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy, which randomly assigned 1,298 patients with breast cancer in a one-to-one ratio to receive tamoxifen only (n = 647) or tamoxifen plus ovarian function suppression (n = 635). The primary endpoint was disease-free survival and the secondary endpoint was overall survival.

Earlier ASTRRA analysis at 5-year follow-up had shown disease-free survival rates of 89.9% for tamoxifen plus ovarian function suppression versus 87.2% for tamoxifen alone in women with hormone-sensitive breast cancer who remained premenopausal or had premenopausal status restored after chemotherapy. Overall survival, a secondary endpoint, also favored adding ovarian function suppression (HR, 0.31; 95% CI, 0.10-0.94; P = .029). The absolute difference for disease-free survival adding ovarian function suppression at the later median follow-up of 106.4 months was 5.2%. The difference at 5 years had been 2.7%, Dr. Kim pointed out. Also, these findings were calculated from time of enrollment. When calculated from time of randomization, the disease-free survival rates were 84.1% and 78.1%, respectively, for tamoxifen plus ovarian function suppression and tamoxifen alone, with a 6.0% absolute difference (HR, 0.67; 95% CI, 0.516-0.872); P = .0025).

The benefit of adding ovarian function suppression to tamoxifen for the secondary endpoint of overall survival at 8 years (96.5% versus 95.3%) did not achieve statistical significance (HR, 0.78; 95% CI, 0.486-1.253); P = .3). “Although it’s not statistically significant, there are absolute differences between the two groups favoring tamoxifen plus ovarian function suppression,” Dr. Kim said in an interview. She pointed out also that for distant metastasis-free survival the hazard ratio was 0.71, significantly favoring tamoxifen plus ovarian function suppression. “More than 95% were still surviving at 8 years with tamoxifen plus ovarian function suppression. So, we need more events to fully evaluate the overall survival benefit.”

A study limitation, Dr. Kim acknowledged in the interview, is that safety and adverse event data were not collected. “As ovarian function suppression has been widely used in clinical practice for decades, and the side effects of its relatively short-term use were considered to be well-understood in previous studies, we focused on the oncologic efficacy of ovarian function suppression in this study,” she said.

Eight-year follow-up of the ASTRRA trial confirmed and extended support for adding 2 years of ovarian function suppression with goserelin to tamoxifen, compared with tamoxifen alone.

“Adding ovarian suppression to tamoxifen should be considered for this population of women,” said senior author Hee Jeong Kim, MD, a breast cancer surgeon with the Asan Medical Center, Seoul, South Korea. Dr. Kim presented the data earlier this month at the annual meeting of the American Society of Clinical Oncology.

The median disease-free survival rate of 85.4% for tamoxifen plus ovarian function suppression versus 80.2% for tamoxifen alone (HR, 0.67; 95% confidence interval, 0.514-0.869; P = .0027) was consistent with recent findings from SOFT (Suppression of Ovarian Function Trial), which also showed a clear survival benefit in breast cancer events with the addition of ovarian function suppression to tamoxifen for women who remain premenopausal after chemotherapy. SOFT trial analyses of disease-free survival at 5 and 8 years demonstrated hazard ratios of 0.82 and 0.76 respectively.

Dr. Kim’s study is a post-trial follow-up of the ASTRRA trial, or the Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy, which randomly assigned 1,298 patients with breast cancer in a one-to-one ratio to receive tamoxifen only (n = 647) or tamoxifen plus ovarian function suppression (n = 635). The primary endpoint was disease-free survival and the secondary endpoint was overall survival.

Earlier ASTRRA analysis at 5-year follow-up had shown disease-free survival rates of 89.9% for tamoxifen plus ovarian function suppression versus 87.2% for tamoxifen alone in women with hormone-sensitive breast cancer who remained premenopausal or had premenopausal status restored after chemotherapy. Overall survival, a secondary endpoint, also favored adding ovarian function suppression (HR, 0.31; 95% CI, 0.10-0.94; P = .029). The absolute difference for disease-free survival adding ovarian function suppression at the later median follow-up of 106.4 months was 5.2%. The difference at 5 years had been 2.7%, Dr. Kim pointed out. Also, these findings were calculated from time of enrollment. When calculated from time of randomization, the disease-free survival rates were 84.1% and 78.1%, respectively, for tamoxifen plus ovarian function suppression and tamoxifen alone, with a 6.0% absolute difference (HR, 0.67; 95% CI, 0.516-0.872); P = .0025).

The benefit of adding ovarian function suppression to tamoxifen for the secondary endpoint of overall survival at 8 years (96.5% versus 95.3%) did not achieve statistical significance (HR, 0.78; 95% CI, 0.486-1.253); P = .3). “Although it’s not statistically significant, there are absolute differences between the two groups favoring tamoxifen plus ovarian function suppression,” Dr. Kim said in an interview. She pointed out also that for distant metastasis-free survival the hazard ratio was 0.71, significantly favoring tamoxifen plus ovarian function suppression. “More than 95% were still surviving at 8 years with tamoxifen plus ovarian function suppression. So, we need more events to fully evaluate the overall survival benefit.”

A study limitation, Dr. Kim acknowledged in the interview, is that safety and adverse event data were not collected. “As ovarian function suppression has been widely used in clinical practice for decades, and the side effects of its relatively short-term use were considered to be well-understood in previous studies, we focused on the oncologic efficacy of ovarian function suppression in this study,” she said.

A new study shows that being overweight may offer some women undergoing treatment for breast cancer protection against neutropenia – a potentially deadly outcome that can occur as a result of chemotherapy treatment.

The study was presented at the annual meeting of the American Society of Clinical Oncology.

It is known that body mass index can affect breast cancer risk and prognosis, but it is not known if BMI can affect how well endocrine therapy works in a given patient. In the PALLAS clinical trial, Georg Pfeiler, MD, Medical University of Vienna, and colleagues, conducted an analysis of 5,698 patients with early hormone receptor–positive breast cancer receiving endocrine therapy with or without palbociclib. Dr. Pfeiler found that women who are overweight or obese had significantly less frequent and less severe cases of neutropenia. With fewer or less severe cases of neutropenia, there were also fewer interruptions in palbociclib treatment.

“One explanation for the lower discontinuation rates may be that the distributional volume of the drug is higher in overweight and obese patients leading to lower serum drug concentrations. It could also be influenced by differences in pharmacokinetics with respect to hyperinsulinemia,” said Dr. Pfeiler, who leads the Oncological Breast Outpatient Clinic and Bone Health Outpatient Clinic at the Medical University of Vienna.

The PALLAS trial compared the combination of palbociclib and adjuvant endocrine therapy with endocrine therapy alone in 5,698 women with early breast cancer. Patients were categorized according to BMI as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (BMI, 25-29.9), and obese (> 30). The investigators analyzed differences in adverse events, time to early discontinuation of palbociclib, and in time to invasive disease-free survival.

At baseline, of 5,698 patients, 68 (1.2%) were underweight, 2,082 (36.5%) were of normal weight, 1,818 (31.9%) were overweight, and, 1,730 (30.4%) were obese. In patients treated with palbociclib, neutropenia was the primary toxicity leading to treatment discontinuation with rates of 21.1% in normal-weight patients, 14.0% of overweight patients, and 5.9% of obese patients, respectively.

Significantly different rates of all-grade neutropenia were observed in normal weight, overweight, and obese participants with regard to total (88.5%, 85.7% and 74.7%), as well as grade 3 (64.1%, 62.0% and 43.9%) and grade 4 neutropenia (7.0%, 3.6% and 2.0%), respectively. The lower frequency and severity of neutropenia observed in overweight and obese patients was associated with a significantly lower treatment discontinuation rate over time when compared with normal-weight patients (overweight vs. normal weight: HR, 0.73; 95% CI 0.63-0.84; P < .0001, and obese vs. normal weight: HR, 0.65; 95% CI, 0.56-0.75; P < .0001). There was, however, despite these observations, no statistically significant improvement in invasive disease survival with the addition of palbociclib to endocrine therapy in any weight category (normal weight: HR, 0.84; 95% CI 0.63-1.12; overweight: HR, 1.10; 95% CI 0.82-1.49; and obese: HR, 0.95; 95% CI, 0.69-1.30).

“This is an early analysis, and should be interpreted with caution, especially with regard to disease outcomes. The findings may reduce concerns over hematologic side effects in the overweight and obese. In the future there may be an important impact if it turns out after longer-term follow-up that palbociclib has been underdosed in the overweight and obese. We may need BMI-adapted dose management,” said Dr. Pfeiler, who is currently working on a longer-term follow-up study of the PALLAS group.

The analysis found no significant correlation between weight and occurrence of invasive disease events.

Dr. Pfeiler disclosed honoraria and grants from Pfizer. The study was funded by Alliance Foundation Trials.

A new study shows that being overweight may offer some women undergoing treatment for breast cancer protection against neutropenia – a potentially deadly outcome that can occur as a result of chemotherapy treatment.

The study was presented at the annual meeting of the American Society of Clinical Oncology.

It is known that body mass index can affect breast cancer risk and prognosis, but it is not known if BMI can affect how well endocrine therapy works in a given patient. In the PALLAS clinical trial, Georg Pfeiler, MD, Medical University of Vienna, and colleagues, conducted an analysis of 5,698 patients with early hormone receptor–positive breast cancer receiving endocrine therapy with or without palbociclib. Dr. Pfeiler found that women who are overweight or obese had significantly less frequent and less severe cases of neutropenia. With fewer or less severe cases of neutropenia, there were also fewer interruptions in palbociclib treatment.

“One explanation for the lower discontinuation rates may be that the distributional volume of the drug is higher in overweight and obese patients leading to lower serum drug concentrations. It could also be influenced by differences in pharmacokinetics with respect to hyperinsulinemia,” said Dr. Pfeiler, who leads the Oncological Breast Outpatient Clinic and Bone Health Outpatient Clinic at the Medical University of Vienna.

The PALLAS trial compared the combination of palbociclib and adjuvant endocrine therapy with endocrine therapy alone in 5,698 women with early breast cancer. Patients were categorized according to BMI as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (BMI, 25-29.9), and obese (> 30). The investigators analyzed differences in adverse events, time to early discontinuation of palbociclib, and in time to invasive disease-free survival.

At baseline, of 5,698 patients, 68 (1.2%) were underweight, 2,082 (36.5%) were of normal weight, 1,818 (31.9%) were overweight, and, 1,730 (30.4%) were obese. In patients treated with palbociclib, neutropenia was the primary toxicity leading to treatment discontinuation with rates of 21.1% in normal-weight patients, 14.0% of overweight patients, and 5.9% of obese patients, respectively.

Significantly different rates of all-grade neutropenia were observed in normal weight, overweight, and obese participants with regard to total (88.5%, 85.7% and 74.7%), as well as grade 3 (64.1%, 62.0% and 43.9%) and grade 4 neutropenia (7.0%, 3.6% and 2.0%), respectively. The lower frequency and severity of neutropenia observed in overweight and obese patients was associated with a significantly lower treatment discontinuation rate over time when compared with normal-weight patients (overweight vs. normal weight: HR, 0.73; 95% CI 0.63-0.84; P < .0001, and obese vs. normal weight: HR, 0.65; 95% CI, 0.56-0.75; P < .0001). There was, however, despite these observations, no statistically significant improvement in invasive disease survival with the addition of palbociclib to endocrine therapy in any weight category (normal weight: HR, 0.84; 95% CI 0.63-1.12; overweight: HR, 1.10; 95% CI 0.82-1.49; and obese: HR, 0.95; 95% CI, 0.69-1.30).

“This is an early analysis, and should be interpreted with caution, especially with regard to disease outcomes. The findings may reduce concerns over hematologic side effects in the overweight and obese. In the future there may be an important impact if it turns out after longer-term follow-up that palbociclib has been underdosed in the overweight and obese. We may need BMI-adapted dose management,” said Dr. Pfeiler, who is currently working on a longer-term follow-up study of the PALLAS group.

The analysis found no significant correlation between weight and occurrence of invasive disease events.

Dr. Pfeiler disclosed honoraria and grants from Pfizer. The study was funded by Alliance Foundation Trials.

A new study shows that being overweight may offer some women undergoing treatment for breast cancer protection against neutropenia – a potentially deadly outcome that can occur as a result of chemotherapy treatment.

The study was presented at the annual meeting of the American Society of Clinical Oncology.

It is known that body mass index can affect breast cancer risk and prognosis, but it is not known if BMI can affect how well endocrine therapy works in a given patient. In the PALLAS clinical trial, Georg Pfeiler, MD, Medical University of Vienna, and colleagues, conducted an analysis of 5,698 patients with early hormone receptor–positive breast cancer receiving endocrine therapy with or without palbociclib. Dr. Pfeiler found that women who are overweight or obese had significantly less frequent and less severe cases of neutropenia. With fewer or less severe cases of neutropenia, there were also fewer interruptions in palbociclib treatment.

“One explanation for the lower discontinuation rates may be that the distributional volume of the drug is higher in overweight and obese patients leading to lower serum drug concentrations. It could also be influenced by differences in pharmacokinetics with respect to hyperinsulinemia,” said Dr. Pfeiler, who leads the Oncological Breast Outpatient Clinic and Bone Health Outpatient Clinic at the Medical University of Vienna.

The PALLAS trial compared the combination of palbociclib and adjuvant endocrine therapy with endocrine therapy alone in 5,698 women with early breast cancer. Patients were categorized according to BMI as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (BMI, 25-29.9), and obese (> 30). The investigators analyzed differences in adverse events, time to early discontinuation of palbociclib, and in time to invasive disease-free survival.

At baseline, of 5,698 patients, 68 (1.2%) were underweight, 2,082 (36.5%) were of normal weight, 1,818 (31.9%) were overweight, and, 1,730 (30.4%) were obese. In patients treated with palbociclib, neutropenia was the primary toxicity leading to treatment discontinuation with rates of 21.1% in normal-weight patients, 14.0% of overweight patients, and 5.9% of obese patients, respectively.

Significantly different rates of all-grade neutropenia were observed in normal weight, overweight, and obese participants with regard to total (88.5%, 85.7% and 74.7%), as well as grade 3 (64.1%, 62.0% and 43.9%) and grade 4 neutropenia (7.0%, 3.6% and 2.0%), respectively. The lower frequency and severity of neutropenia observed in overweight and obese patients was associated with a significantly lower treatment discontinuation rate over time when compared with normal-weight patients (overweight vs. normal weight: HR, 0.73; 95% CI 0.63-0.84; P < .0001, and obese vs. normal weight: HR, 0.65; 95% CI, 0.56-0.75; P < .0001). There was, however, despite these observations, no statistically significant improvement in invasive disease survival with the addition of palbociclib to endocrine therapy in any weight category (normal weight: HR, 0.84; 95% CI 0.63-1.12; overweight: HR, 1.10; 95% CI 0.82-1.49; and obese: HR, 0.95; 95% CI, 0.69-1.30).

“This is an early analysis, and should be interpreted with caution, especially with regard to disease outcomes. The findings may reduce concerns over hematologic side effects in the overweight and obese. In the future there may be an important impact if it turns out after longer-term follow-up that palbociclib has been underdosed in the overweight and obese. We may need BMI-adapted dose management,” said Dr. Pfeiler, who is currently working on a longer-term follow-up study of the PALLAS group.

The analysis found no significant correlation between weight and occurrence of invasive disease events.

Dr. Pfeiler disclosed honoraria and grants from Pfizer. The study was funded by Alliance Foundation Trials.

When a patient first presents to a doctor with signs and symptoms of having breast cancer that has metastasized to other parts of the body, the prospects of long-term survival are dim. But now, a new study presented at the annual meeting of the American Society of Clinical Oncology suggests that women with metastatic HER2+ breast cancer are generally living longer, compared with women treated in previous years.

Between 2010 and 2018, the overall survival for 5,576 women (99% women) with HER2+ metastatic breast cancer enrolled in this study improved 5.6% each year of the study. The study also showed a 6.4% improvement in breast cancer–specific death rates year over year.

“These highlights coincide with significant therapeutic advances for HER2+ metastatic breast cancer over the past decade. We need to continue our research efforts to identify better treatments for our patients so we can continue to improve the prognosis of these patients,” said study author Jose Pablo Leone, MD, a medical oncologist with Dana-Farber Cancer Institute, Boston.

The study, which is based on an evaluation of data from the Surveillance, Epidemiology and End Results database, found factors associated with shorter survival included older age, Black race, lower income, and the presence of visceral or brain metastases. Long-term survival of more than 5 years was associated with younger age, White race, and higher income, but also having fewer metastatic sites and estrogen receptor (ER)/progesterone receptor (PR) positivity.

“We also found specific factors that were only associated with shorter overall survival, such as the presence of metastases in the brain, liver, or lung. The lack of metastasis in these sites was not associated with longer overall survival. In contrast, a lower number of metastatic sites, regardless of the location of those sites were associated with longer overall survival but not short-term survival,” Dr. Leone said.

A total of 63.3% of patients in the study survived less than 2 years while 37.8% lived 5 years or more, and 26.8% lived longer than 8 years. Factors associated with less than 2 years in overall survival were older age (odds ratio, 3.76), Black race (OR 1.5), nonductal nonlobular (OR, 4.64), brain metastases (OR, 2.95), liver metastases (OR, 1.98), lung metastases (OR, 1.56), ER/PR negativity (OR, 1.74), and lower income (OR, 1.62). Factors associated with longer survival of 5 years or more included younger age (OR, 2.85), White race (OR, 1.7), fewer metastatic organ sites (OR, 2.6), ER/PR positivity (OR, 1.27), and higher income (OR, 3.31).

Dr. Leone said that, while involvement of specific visceral sites (brain, liver, lung) was associated with shorter overall survival, the odds of living longer than 5 years was not associated with those sites. In contrast, the number of sites was associated with longer overall survival, but not shorter overall survival regardless of location. “While fewer number of metastatic sites were associated with higher odds of overall survival greater than 5 years, the number of metastatic sites was not associated with the odds of overall survival of being less than 2 years,” he said.

A limitation of the study included the retrospective nature of the study. “Treatment data are unavailable, so we cannot quantify the impact of various treatments on the odds of survival,” Dr. Leone said.

This study was not funded.

When a patient first presents to a doctor with signs and symptoms of having breast cancer that has metastasized to other parts of the body, the prospects of long-term survival are dim. But now, a new study presented at the annual meeting of the American Society of Clinical Oncology suggests that women with metastatic HER2+ breast cancer are generally living longer, compared with women treated in previous years.

Between 2010 and 2018, the overall survival for 5,576 women (99% women) with HER2+ metastatic breast cancer enrolled in this study improved 5.6% each year of the study. The study also showed a 6.4% improvement in breast cancer–specific death rates year over year.

“These highlights coincide with significant therapeutic advances for HER2+ metastatic breast cancer over the past decade. We need to continue our research efforts to identify better treatments for our patients so we can continue to improve the prognosis of these patients,” said study author Jose Pablo Leone, MD, a medical oncologist with Dana-Farber Cancer Institute, Boston.

The study, which is based on an evaluation of data from the Surveillance, Epidemiology and End Results database, found factors associated with shorter survival included older age, Black race, lower income, and the presence of visceral or brain metastases. Long-term survival of more than 5 years was associated with younger age, White race, and higher income, but also having fewer metastatic sites and estrogen receptor (ER)/progesterone receptor (PR) positivity.

“We also found specific factors that were only associated with shorter overall survival, such as the presence of metastases in the brain, liver, or lung. The lack of metastasis in these sites was not associated with longer overall survival. In contrast, a lower number of metastatic sites, regardless of the location of those sites were associated with longer overall survival but not short-term survival,” Dr. Leone said.

A total of 63.3% of patients in the study survived less than 2 years while 37.8% lived 5 years or more, and 26.8% lived longer than 8 years. Factors associated with less than 2 years in overall survival were older age (odds ratio, 3.76), Black race (OR 1.5), nonductal nonlobular (OR, 4.64), brain metastases (OR, 2.95), liver metastases (OR, 1.98), lung metastases (OR, 1.56), ER/PR negativity (OR, 1.74), and lower income (OR, 1.62). Factors associated with longer survival of 5 years or more included younger age (OR, 2.85), White race (OR, 1.7), fewer metastatic organ sites (OR, 2.6), ER/PR positivity (OR, 1.27), and higher income (OR, 3.31).

Dr. Leone said that, while involvement of specific visceral sites (brain, liver, lung) was associated with shorter overall survival, the odds of living longer than 5 years was not associated with those sites. In contrast, the number of sites was associated with longer overall survival, but not shorter overall survival regardless of location. “While fewer number of metastatic sites were associated with higher odds of overall survival greater than 5 years, the number of metastatic sites was not associated with the odds of overall survival of being less than 2 years,” he said.

A limitation of the study included the retrospective nature of the study. “Treatment data are unavailable, so we cannot quantify the impact of various treatments on the odds of survival,” Dr. Leone said.

This study was not funded.

When a patient first presents to a doctor with signs and symptoms of having breast cancer that has metastasized to other parts of the body, the prospects of long-term survival are dim. But now, a new study presented at the annual meeting of the American Society of Clinical Oncology suggests that women with metastatic HER2+ breast cancer are generally living longer, compared with women treated in previous years.

Between 2010 and 2018, the overall survival for 5,576 women (99% women) with HER2+ metastatic breast cancer enrolled in this study improved 5.6% each year of the study. The study also showed a 6.4% improvement in breast cancer–specific death rates year over year.

“These highlights coincide with significant therapeutic advances for HER2+ metastatic breast cancer over the past decade. We need to continue our research efforts to identify better treatments for our patients so we can continue to improve the prognosis of these patients,” said study author Jose Pablo Leone, MD, a medical oncologist with Dana-Farber Cancer Institute, Boston.

The study, which is based on an evaluation of data from the Surveillance, Epidemiology and End Results database, found factors associated with shorter survival included older age, Black race, lower income, and the presence of visceral or brain metastases. Long-term survival of more than 5 years was associated with younger age, White race, and higher income, but also having fewer metastatic sites and estrogen receptor (ER)/progesterone receptor (PR) positivity.

“We also found specific factors that were only associated with shorter overall survival, such as the presence of metastases in the brain, liver, or lung. The lack of metastasis in these sites was not associated with longer overall survival. In contrast, a lower number of metastatic sites, regardless of the location of those sites were associated with longer overall survival but not short-term survival,” Dr. Leone said.

A total of 63.3% of patients in the study survived less than 2 years while 37.8% lived 5 years or more, and 26.8% lived longer than 8 years. Factors associated with less than 2 years in overall survival were older age (odds ratio, 3.76), Black race (OR 1.5), nonductal nonlobular (OR, 4.64), brain metastases (OR, 2.95), liver metastases (OR, 1.98), lung metastases (OR, 1.56), ER/PR negativity (OR, 1.74), and lower income (OR, 1.62). Factors associated with longer survival of 5 years or more included younger age (OR, 2.85), White race (OR, 1.7), fewer metastatic organ sites (OR, 2.6), ER/PR positivity (OR, 1.27), and higher income (OR, 3.31).

Dr. Leone said that, while involvement of specific visceral sites (brain, liver, lung) was associated with shorter overall survival, the odds of living longer than 5 years was not associated with those sites. In contrast, the number of sites was associated with longer overall survival, but not shorter overall survival regardless of location. “While fewer number of metastatic sites were associated with higher odds of overall survival greater than 5 years, the number of metastatic sites was not associated with the odds of overall survival of being less than 2 years,” he said.

A limitation of the study included the retrospective nature of the study. “Treatment data are unavailable, so we cannot quantify the impact of various treatments on the odds of survival,” Dr. Leone said.

This study was not funded.