Survival of veterans treated with enzalutamide and abiraterone for metastatic castrate resistant prostate cancer based on comorbid diseases.

BACKGROUND: Comorbid diseases influence patient outcomes, yet little is known about how comorbidities interact with treatments for metastatic castrate-resistant prostate cancer (mCRPC). No head-to-head trials have compared the efficacy of abiraterone and enzalutamide - oral androgen-receptor targeted agents (ARTAs) for mCRPC. In patients with comorbid disease, outcomes with ARTAs may differ due to disparate mechanisms of action, adverse events, and drug interactions. METHODS: Retrospective observational study of US veterans initiating treatment for mCRPC with abiraterone or enzalutamide between September 2014 and June 2017. Treatment duration and overall survival (OS) was compared based on age and comorbid diseases. The association between ARTA and OS was assessed using Cox proportional hazards and propensity-score matched modeling while adjusting for potential confounders. Sensitivity analyses were performed based on patient age, comorbidities, and subsequent treatments for mCRPC. RESULTS: Of 5822 veterans treated for mCRPC, 43.0% initially received enzalutamide and 57.0% abiraterone. Veterans initially treated with enzalutamide versus abiraterone were older (mean 75.8 vs. 75.0 years) with higher mean Charlson comorbidity index (4.4 vs. 4.1), and higher rates of cardiovascular disease or diabetes (74.2% vs. 70.6%). In the entire population, veterans initially treated with enzalutamide had longer median OS compared to those initially treated with abiraterone (24.2 vs. 22.1 months, p = 0.001). In veterans with cardiovascular disease or diabetes, median treatment duration with enzalutamide was longer (11.4 vs. 8.6 months, p < 0.001) with longer median OS compared to abiraterone (23.2 vs. 20.5 months, p < 0.001). In a propensity score matched cohort, enzalutamide was associated with decreased mortality compared to abiraterone (HR 0.90, 95% CI 0.84-0.96). CONCLUSIONS: Veterans with cardiovascular disease or diabetes had longer treatment duration and OS with enzalutamide compared to abiraterone. Further study of ARTA selection may benefit men with metastatic castrate resistant prostate cancer and likely hormone sensitive prostate cancer, especially among patients with comorbid diseases.

Treating advanced lung cancer in older veterans with comorbid conditions and frailty.

Advanced lung cancer is a deadly malignancy that is a common cause of death among Veterans. Significant advancements in lung cancer therapeutics have been made over the past decade and survival outcomes have improved. The Veteran population is older, has more medical comorbidities and frailty compared to the general population. These factors must be accounted for when evaluating patients for treatment and selecting treatment options. This article explores the impact of these important issues in the management of advanced lung cancer. Recent clinical trials leading to the approval of modern therapies will be outlined and treatment outcomes specific to older patients discussed. The impact of key comorbidities that are common in Veterans and their impact on lung cancer treatment will be reviewed. There is no gold standard frailty index for assessment of frailty in patients with advanced lung cancer and the ability to predict tolerability and benefit from systemic therapies. Currently available systemic therapies are associated with higher risk of adverse events and lower potential for clinically meaningful improvement in outcomes. Future research needs to focus on designing better frailty indices and developing novel therapies that are safer and more effective therapies for frail patients, who constitute a considerable proportion of individuals diagnosed with lung cancer.