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Treatment with enzalutamide (Xtandi) was associated with an overall survival (OS) benefit compared with abiraterone acetate (Zytiga) among United States veterans with metastatic castration-resistant prostate cancer (mCRPC), according to a retrospective analysis shared during the 2021 ASCO Annual Meeting.1
In the overall population, the median OS was 24.1 months with enzalutamide versus 22.2 months with abiraterone (P = .003); however, this modest OS benefit was more pronounced among patients who received only 1 treatment (median OS, 18.9 months vs 13.6 months, respectively [P <.001]).
In contrast, among patients who received 2 or more treatments, there was no difference in median OS: 28.0 months versus 27.9 months, respectively (P = .24). Of note, patients receiving 1 treatment were generally older (mean age, 78.3 vs 73.2 years) and had more comorbidities (median Elixhauser Comorbidity Index score, 6.4 vs 5.7) compared with patients who received ≥2 treatments.
“In older patients with higher comorbidity burdens who are not candidates for docetaxel, consider using enzalutamide instead of abiraterone,” said lead study author Martin Schoen, MD, an assistant professor of Medicine at St. Louis University and a staff physician at the St. Louis Veterans Affairs Medical Center.
Explaining the investigators’ rationale for conducting the study, Schoen said, “Both abiraterone and enzalutamide are used to treat metastatic castrate resistant prostate cancer, but no head-to-head trials have been performed, and these agents are commonly used in older patients with medical comorbidities. So we wanted to identify differences in survival in veterans across the country.”
The study included 5895 men with mCRPC treated with abiraterone or enzalutamide in the Veterans Health Administration between September 10, 2014, and June 3, 2017. Follow-up went to April 2020.
Overall, 43.5% (n = 2562) of patients initially received enzalutamide and 56.5% (n = 3333) initially received abiraterone. The mean age in the enzalutamide arm was 75.9 years compared with 75 years in the abiraterone arm. The mean comorbidity scores on the Elixhauser Comorbidity Index were 6.2 versus 5.9, respectively.
Patients initially treated with abiraterone were more likely to have received docetaxel (28.4% vs 24.1%) and both abiraterone and enzalutamide (51% vs 45.2%). Overall, 2578 patients received only 1 treatment and 3317 patients received ≥2 treatments.
When using statistical models to adjust for age and comorbidity, there was a 13% (HR, 0.87; P <.001) reduced risk of death with enzalutamide versus abiraterone. This reduction in risk went up to 27% (HR, 0.73; P <.001) in patients who received only enzalutamide or abiraterone and no docetaxel. The risk of death was the same among patients receiving ≥2 treatments.
Regarding next steps with this research, Schoen said, “In the future, we would like to prospectively define patients with mCRPC who benefit from enzalutamide based on comorbidities and concomitant medications and would also like to determine if this association is also present in patients with metastatic hormone-sensitive prostate cancer.
1. Schoen MW, Carson KR , Luo S. Survival of veterans treated with enzalutamide and abiraterone in advanced prostate cancer. J Clin Oncol 39, 2021 (suppl 15; abstr 5032).