Joshi J. Alumkal, MD
Invited discussant of the ACIS study, Joshi J. Alumkal, MD, leader of the Genitourinary Medical Oncology Section at the University of Michigan Rogel Cancer Center, noted that the toxicities were slightly higher with apalutamide plus abiraterone acetate/prednisone, including fatigue, hypertension, skin rash, cardiac disorders, and grade 3 and 4 events.
“The study was well conducted but had limitations. Despite the improvement in radiographic progression-free survival on study, there was no improvement in overall survival. Furthermore, second radiographic progression-free survival—defined as the time from study enrollment to progression on the first subsequent agent used after progression on study—appeared similar between groups. This suggests subsequent therapy worked less well in patients enrolled on the apalutamide plus abiraterone acetate/prednisone combination arm vs those enrolled on the abiraterone/prednisone only arm. The lack of overall survival benefit or second radiographic progression-free survival benefit in other studies, including the ALLIANCE A031201 study that failed to show a benefit with combining androgen receptor–signaling inhibitors vs a single-agent androgen receptor–signaling inhibitor, raises questions about the utility of combining drugs that target the androgen receptor in men with castration-resistant prostate cancer,” Dr. Alumkal told listeners.
“We need more mature data from this trial. At this time, I do not believe that ACIS results should change practice,” Dr. Alumkal commented. Because castration-resistant prostate cancer is not just one disease, and tumors from individual patients clearly responded differently, Dr. Alumkal closed his discussion with this comment: “The key question as we return to the clinic is what is the tumor biology in the patient sitting before us? It is critical to understand that to move the needle on outcomes for patients with castration-resistant prostate cancer, especially those resistant to androgen receptor–signaling inhibitors.
DISCLOSURE: Dr. Alumkal has served as a consultant or advisor to Dendreon and Merck Sharp & Dohme; has received institutional research funding from Aragon Pharmaceuticals, Astellas Pharma, Gilead Sciences, and Zenith Epigenetics; has been reimbursed for travel, accommodations, or other expenses by Astellas Pharma and Merck Sharp & Dohme; and has held other relationships with Astellas Pharma.
The phase III ACIS trial met its primary endpoint at 6 months showing that apalutamide plus abiraterone acetate/prednisone (AAP) extended radiographic progression-free survival vs abiraterone acetate/prednisone alone in patients with chemotherapy-naive metastatic castration-resistant prostate...