The following article features coverage from the American Urological Association (AUA) 2021 annual meeting. Click here to read more of Cancer Therapy Advisor’s conference coverage.

The combination of pembrolizumab and olaparib demonstrated antitumor activity and acceptable safety for men with molecularly unselected, docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC) after a minimum of 11.4 months of follow-up, according to data presented at the American Urological Association (AUA) 2021 Virtual Experience.

The nonrandomized, multicenter, multicohort, open-label, phase 1b/2 KEYNOTE-365 trial ( Identifier: NCT02861573) evaluated the safety, tolerability, and efficacy of pembrolizumab combination therapy in men with mCRPC. Researchers presented updated safety and efficacy results after previously reported findings revealed that pembrolizumab plus olaparib demonstrated promising antitumor activity and acceptable safety in molecularly unselected patients treated with docetaxel for mCRPC.

Cohort A included patients with mCRPC previously treated with docetaxel with 1 other chemotherapy (≤2 next-generation hormonal agents). Treatment with pembrolizumab was administered on day 1 of each 3-week dosing cycle for as many as 35 cycles (~2 years). Olaparib 400 mg capsules for the first 41 patients or 300 mg oral twice daily tablets were given continuously from day 1.

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Treatment continued until confirmed disease progression, unacceptable toxicity, or withdrawal of consent. Participants who discontinued 1 drug owing to treatment-related adverse events (TRAEs) were allowed to continue the other drug until discontinuation criteria were met.

The median follow up as of November 12, 2020, was 19.3 months (range, 11.4-45.9 months). A total of 104 patients were enrolled, 102 were treated, and 92 discontinued treatment largely owing to progressive disease (51.0%). Participants’ median age was 69.5 years (range, 47-84), 28.4% were PD-L1-positive, 33.3% had visceral disease, and 56.9% had measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.

The confirmed prostate-specific antigen (PSA) response rate in the cohort was 14.7% (95% CI, 8.5-23.1), and the median time to PSA progression was 4.0 months (3.0-4.9). Among the 58 patients who had measurable disease, the confirmed objective response rate (ORR) was 6.9% (1.9-16.7; 4 partial responses). The median duration of response (DOR) was not achieved (range, 7.2+ to 37.8+ months), and 2 patients had a response 12 months or longer.

For the full cohort, the disease control rate was 26.5% (95% CI, 18.2-36.1). The median radiographic progression-free survival (rPFS) was 5.2 months (4.1-6.5), and the median overall survival was 14.4 months (10.4-17.9).

Treatment-related adverse events (TRAEs) were recorded in 93 patients (91.2%), and the most commonly occurring (≥30%) were anemia (41.2%), nausea (41.2%), decreased appetite (30.4%), and fatigue (30.4%). Grades 3 to 5 TRAEs were observed in 49 patients (48.0%), with anemia being the most common (27.5%). A total of 6 patients (5.9%) died from AEs, 2 of which were treatment related.

Any reduction in target lesion size was observed in 58.6% of patients, and 17.2% had a reduction of 30% or more. The safety and tolerability profile of the combination therapy was consistent with the profiles for each agent, noted the study authors.

“The promising rPFS and overall survival data support further evaluation of pembrolizumab + olaparib in molecularly unselected patients with mCRPC who previously received docetaxel treatment,” the investigators wrote.

Disclosure: The research was funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.

Read more of Cancer Therapy Advisor’s coverage of AUA 2021 by visiting the conference page.


Nordquist LT, Yu EY, Piulats JM, et al. Pembrolizumab plus olaparib in patients with docetaxel-pretreated metastatic castration-resistant prostate cancer: updated results from KEYNOTE-365 cohort A, with a minimum of 11 months of follow-up for all patients. Presented at: AUA2021 Virtual Experience held September 10-13, 2021. MP24-14.