Pembrolizumab and Olaparib Versus Next-Generation Hormonal Agents in mCRPC

The phase 3 KEYLYNK-010 trial evaluated pembrolizumab plus olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) that progressed after previous treatment with abiraterone or enzalutamide and docetaxel.

According to lead author, Evan Yu, pembrolizumab plus olaparib did not improve survival compared with switching from previous abiraterone to enzalutamide, or vice versa. These findings were presented at the EMSO Congress 2022.

The study enrolled 793 molecularly unselected patients with mCRPC and previous treatment with either next-generation hormonal agent (NHA) across 3 treatment groups:

• pembrolizumab 200 mg intravenously once every 3 weeks for 35 cycles plus olaparib 300 mg orally twice daily
• abiraterone 1000 mg orally once daily if previous NHA was enzalutamide
• enzalutamide 160 mg orally once daily if previous NHA was abiraterone

Primary outcomes were radiographic progression-free survival (rPFS) or overall survival (OS), and secondary outcomes included objective response rate (ORR) and safety according to adverse events.

The authors reported that neither primary outcome was met over a median follow-up of 11.9 months (range, 0.9-31.0). Specifically, pembrolizumab plus olaparib yielded a median rPFS of 4.4 months versus 4.2 months with NHAs (hazard ratio [HR], 1.02; 95% CI, 0.82-1.25; P=.55) and a median OS of 15.8 months versus 14.6 months with NHAs (HR, 0.94; 95% CI, 0.77-1.14; P=.26).

Further subgroup analyses identified a potential improvement in rPFS with pembrolizumab and olaparib among patients with homologous recombination repair gene alteration (HR, 0.53; 95% CI, 0.33-0.86) versus those without (HR, 1.19; 95% CI, 0.90-1.58); however, no benefits were seen for OS between the 2 subgroups.

Grade 3 or higher treatment-related adverse events were reported in 35% of patients in the pembrolizumab plus olaparib group compared with 9% in the NHA groups. Pembrolizumab plus olaparib exhibited an ORR of 17% compared with 6% on NHAs (nominal P=.002).

Ultimately, the study was ended prematurely due to futility, and the authors concluded that pembrolizumab and olaparib, despite a higher response rate, did not improve survival compared with alternating from the previously used NHA in patients with mCRPC.