Sherene Loi, MD, of Peter MacCallum Cancer Centre, Melbourne, Australia, said that the BROCADE3 trial was positive because it met its primary endpoint. However, she expressed some reservations about adopting this combination as a new standard for HER2-negative BRCA-mutated advanced breast cancer.

Sherene Loi, MD

“BROCADE3 was designed for the germline BRCA population. This was largely first-line treatment for a population with minimal platinum exposure. The addition of veliparib did add some toxicity, and toxicity is important. There were higher rates of thrombocytopenia, anemia, and alopecia. I would have liked to see patient-reported outcomes for the trial. Survival data are immature, but survival of 33 months is long for this population,” Dr. Loi said. “The curves look remarkably similar to those for olaparib and carboplatin in ovarian cancer.”

Words of Caution

Dr. Loi continued: “It’s not clear that this combination will become the new standard for germline-mutated advanced breast cancer. The progression-free survival improvement was modest, and there were high response rates and clinical benefit rates in both arms. It’s not clear whether the survival benefit was due to the combination. At present, the guidelines advise single-agent chemotherapy sequentially in the absence of visceral crises. We await more mature survival data and correlative analyses,” she told listeners.

“There are unanswered questions, such as the best sequencing strategy for germline mutation carriers. The future will bring newer DNA damage–response agents and immunotherapy combinations, which will improve survival and quality of life,” Dr. Loi said.

DISCLOSURE: Dr. Loi reported financial relationships with Bristol-Myers Squibb, Merck, Novartis, Pfizer, Puma Biotechnology, and Roche/Genentech. She has served as an unpaid consultant to Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche/Genentech, and Seattle Genetics.