In cohort D of the KEYNOTE-365 study, safety, and efficacy of the combination of the PD-1 inhibitor, pembrolizumab plus abiraterone acetate and prednisone was assessed in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC). Lead author, Cristiano Ferrario, MD, reported that the triplet therapy exhibited antitumor activity in this population in a presentation of the report during Poster Session A: Prostate Cancer of the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium.
Patients who had not received next-generation hormonal agents (NHAs), or for whom enzalutamide was intolerable or ineffective, received pembrolizumab 200mg IV Q3W, abiraterone acetate 100 mg PO QD, and prednisone 5 mg PO BID. Overall, Dr. Ferrario reported that “78.6% of patients had a reduction in PSA levels from baseline.” The ORR was 16.2%, 7.7%, and 21.7% for patients with RECIST-measurable disease, who received enzalutamide, and who were NHA-naïve, respectively.
Regarding toxicity, 90.3% of patients experienced a treatment-related adverse events (TRAEs), of which 36.8% experienced grade III–V TRAEs. Additionally, 18.4% of patients had a grade III or IV ALT laboratory elevation, and 12.6% had a grade III or IV AST elevation. Overall, five patients died of AEs (one death was treatment related).
Though adverse events were experienced by a large portion of the study’s cohort, Dr. Ferrario advanced that the safety profile was “generally consistent with individual profiles of each agent, although there was an increased incidence of grade 3/4 ALT/AST laboratory elevations than reported for the individual treatments.” Overall, the antitumor activity observed suggests possible advantages for this agent in the treatment of chemotherapy-naïve patients with mCRPC.