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Rucaparib Shows Antitumor Efficacy in mCRPC With Deleterious BRCA Alteration
In a study of patients with metastatic castration-resistant prostate cancer (mCRPC) and deleterious BRCA alteration, rucaparib yielded antitumor activity with manageable safety (J Clin Oncol. 2020 Aug 14. Epub ahead of print).
"BRCA1 or BRCA2 (BRCA) alterations are common in men with [mCRPC] and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors," wrote lead investigator Wassim Abida, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, and colleagues.
The study consisted of 155 patients with BRCA-altered mCRPC whose disease progressed after 1 or 2 lines of next-generation androgen receptor–directed therapy and 1 taxane-based chemotherapy. These patients received rucaparib 600 mg twice daily; the efficacy end point was the objective response rate (ORR) and locally assessed prostate-specific antigen (PSA) response.
The independent radiology review confirmed the ORR to be 43.5% (95% CI, 31.0%-56.7%) whereas the investigator assessment found an ORR of 50.8% (95% CI, 38.1%-63.4%).
The confirmed PSA response rate was 54.8% (95% CI, 45.2% to 64.1%; 61 of 115 patients). In patients with germline or somatic BRCA alteration and BRCA1 or BRCA2 alteration, the ORRs were similar, but patients with a BRCA2 alteration had a higher PSA response rate.
The most common grade ≥3 treatment-emergent adverse event was anemia (25.2%).
"Rucaparib has antitumor activity in patients with mCRPC and a deleterious BRCA alteration, but with a manageable safety profile consistent with that reported in other solid tumor types," concluded Dr Abida et al.—Alexandra Graziano
