Formal discussant of the BRCAAway trial, Kim N. Chi, MD, of the British Columbia Cancer–Vancouver Center, University of British Columbia, Canada, said this study supports the use of PARP inhibitors in patients with metastatic castration-resistant prostate cancer and homologous recombination–repair alterations. “In fact,” he reminded listeners, “this is now the standard of care.”

Kim N. Chi, MD

Dr. Chi continued: “There are lingering questions, including whether combination treatment is better than sequential treatment, the increased cost of combination treatment, and the fact that sequential treatment could result in a loss of opportunity [to get the most powerful treatment] upfront. The crossover data support combination therapy.”

“There are several limitations of the study,” he added. “It is a horse race trial, with few patients. The study population is heavily weighted toward patients with BRCA2, and crossover treatment is only additive. This trial was not designed to compare combination therapy vs sequential therapy,” Dr. Chi stated. “Many patients have aggressive disease and won’t go on to get sequential therapy.”

“This study supports an upfront combination, as in the real world only a few patients with aggressive disease get to have one or two lines of therapy. In clinical practice, give the best treatment upfront,” he told listeners. Dr. Chi added that clinical trials should be designed so “the control arm represents best practice.”

DISCLOSURE: Dr. Chi has received honoraria from Amgen, Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Merck, Novartis, Pfizer, POINT Biopharma, and Roche; has served as a consultant or advisor to Amgen, Astellas Pharma, AstraZeneca, Bayer, Janssen, Merck, POINT Biopharma, and Roche; and has received institutional research funding from Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, ESSA Pharma, Janssen, Merck, Novartis, Pfizer, Roche, and Sanofi.