Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic...

Area of Science:

• Oncology
• Medical research
• Clinical trials

Background:

• Metastatic castration-resistant prostate cancer (mCRPC) presents a significant unmet need for effective therapies, particularly in patients with extensive prior treatment.
• The KEYLYNK-010 study addresses this by evaluating novel treatment combinations in a heavily pretreated mCRPC population.

Purpose of the Study:

• To evaluate the efficacy of pembrolizumab plus olaparib compared to a next-generation hormonal agent (NHA) in patients with previously treated, biomarker-unselected mCRPC.
• To assess radiographic progression-free survival (rPFS) and overall survival (OS) as primary endpoints.

Main Methods:

• Phase III, open-label, randomized study (KEYLYNK-010) involving 529 participants assigned to pembrolizumab plus olaparib and 264 to NHA.
• Participants had mCRPC progressing after abiraterone or enzalutamide and docetaxel.
• Dual primary endpoints: rPFS and OS. Key secondary endpoints included time to first subsequent therapy (TFST) and objective response rate (ORR).

Main Results:

• Pembrolizumab plus olaparib showed no significant improvement in median rPFS (4.4 vs. 4.2 months; HR, 1.02) or median OS (15.8 vs. 14.6 months; HR, 0.94) compared to NHA.
• Median TFST was 7.2 months for pembrolizumab plus olaparib versus 5.7 months for NHA (HR, 0.86).
• Objective response rate was higher with pembrolizumab plus olaparib (16.8%) than NHA (5.9%), but grade ≥3 treatment-related adverse events were more frequent (34.6% vs. 9.0%).

Conclusions:

• Pembrolizumab plus olaparib did not demonstrate a significant benefit in rPFS or OS for biomarker-unselected, heavily pretreated mCRPC patients.
• The study was terminated early due to futility.
• No new safety concerns were identified with the combination therapy.