Dr. Tagawa on Significance of BRCA2 With PSMA-Targeted Radionuclide Therapy in Prostate Cancer

Scott T. Tagawa, MD, Richard A. Stratton Associate Professor in Hematology and Oncology, associate professor of clinical medicine and urology at Weill Cornell Medicine, associate attending physician, NewYork-Presbyterian/Weill Cornell Medical Center, discusses the impact of the BRCA2 mutation in patients with prostate cancer who are receiving prostate-specific membrane antigen (PSMA)—targeted radionuclide therapy.

PSMA is overexpressed on the vast majority of prostate cancer tumors at around 90%, according to Tagawa. Those tumors can be targeted with small molecules or with antibodies and some patients respond very well, while others respond adequately or don’t respond at all, explained Tagawa. A recent retrospective study examined what clinical or genomic factors are associated with respond to resistance.

The study looked at patients who had whole-exome sequencing and saw that patients with BRCA2 mutations and received PSMA-targeted radionuclide therapy were associated with improvements in progression-free survival and overall survival (OS). After expanding the trial to include patients with germline, targeted, somatic, and whole-exome mutations, researchers found the same results within the larger data set. The study concluded that the presence of BRCA2, either germline and/or somatic, was associated with better responses in terms of prostate-specific antigen declines and longer OS. Validation of these findings in larger prospective trials is warranted.