The following is a summary of “Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial,” published in the August 2023 issue of Oncology by Antonarakis, et al.

For a phase III KEYLYNK-010 study, researchers sought to assess the efficacy of pembrolizumab plus olaparib compared to a next-generation hormonal agent (NHA) in patients with heavily pretreated, metastatic castration-resistant prostate cancer (mCRPC).

Patients with mCRPC who had previously progressed on or after treatment with abiraterone or enzalutamide (but not both) and docetaxel were eligible for the study. They were randomly assigned in a 2:1 ratio to receive either pembrolizumab plus olaparib or an NHA (abiraterone or enzalutamide). The primary endpoints were radiographic progression-free survival (rPFS) and overall survival (OS) as assessed by a blinded independent central review per Prostate Cancer Working Group–modified RECIST 1.1. Time to first subsequent therapy (TFST) was a key secondary endpoint. Safety and objective response rate (ORR) were also evaluated as secondary endpoints.

Between May 30, 2019, and July 16, 2021, 529 participants were assigned to pembrolizumab plus olaparib and 264 to the NHA group. The final analysis for rPFS showed that the median rPFS was 4.4 months (95% CI, 4.2 to 6.0) in the pembrolizumab plus olaparib group and 4.2 months (95% CI, 4.0 to 6.1) in the NHA group (hazard ratio [HR], 1.02 [95% CI, 0.82 to 1.25]; P = .55). The final analysis for OS revealed a median OS of 15.8 months (95% CI, 14.6 to 17.0) in the pembrolizumab plus olaparib group and 14.6 months (95% CI, 12.6 to 17.3) in the NHA group (HR, 0.94 [95% CI, 0.77 to 1.14]; P = .26). The final TFST analysis showed a median TFST of 7.2 months (95% CI, 6.7 to 8.1) in the pembrolizumab plus olaparib group and 5.7 months (95% CI, 5.0 to 7.1) in the NHA group (HR, 0.86 [95% CI, 0.71 to 1.03]). The ORR was higher with pembrolizumab plus olaparib than NHA (16.8% vs. 5.9%). Grade ≥3 treatment-related adverse events occurred in 34.6% of participants in the pembrolizumab plus olaparib group and 9.0% in the NHA group.

The combination of pembrolizumab plus olaparib did not significantly improve rPFS or OS compared to using an NHA in patients with biomarker-unselected, heavily pretreated mCRPC. The study was stopped due to a lack of efficacy, but no new safety signals were observed.

Source: ascopubs.org/doi/full/10.1200/JCO.23.00233