Pembrolizumab–Olaparib Combo Effective in Patients With CRPC Previously Treated With Docetaxel

San Francisco, California—Results from a recent clinical trial show that combining pembrolizumab and olaparib therapy in patients with metastatic castration-resistant prostate cancer (CRPC) is effective. Safety results of the combination were also comparable to those seen with pembrolizumab or olaparib monotherapy.

“Activity with pembro[lizumab] or olaparib has been observed in mCRPC pts [patients] who progressed on 2nd-generation hormonal therapy…and chemotherapy,” said Evan Y. Yu, MD, Professor, Department of Medicine, Division of Oncology, University of Washington School of Medicine, Seattle, and colleagues, who conducted the phase 1b/2 KEYNOTE-365 clinical trial to evaluate various combination therapies comprising pembrolizumab and other agents in metastatic CRPC.

Dr Yu and colleagues presented preliminary data from the study specific to recipients of pembrolizumab plus olaparib (cohort A) at the 2019 ASCO Genitourinary Cancers Symposium.

Patients were included in the study if they had metastatic CRPC that progressed in the 6 months before screening, if they previously received docetaxel, and if they had received up to 2 previous 2nd-generation hormone therapies. They could also be included if they had received 1 other chemotherapy.

The primary end points were safety and prostate-specific antigen response rate. The secondary end points included time to PSA progression, radiographic progression-free survival (PFS), and overall survival (OS).

A total of 41 patients (median age, 69 years) were included in the study; 27% were PD-L1–positive, 42% had visceral disease, and 68% had RECIST-measurable disease. All patients received pembrolizumab plus olaparib and were followed-up with for a median of 11 months.

According to the early results of the study, the median time to PSA progression was 16 weeks (95% confidence interval [CI], 14-21); the median radiographic PFS was 5 months (95% CI, 4-8); and the median OS was 14 months (95% CI, 8-not reached).

Overall, 39 (95%) patients had treatment-related adverse events, the most common (≥30%) of which were anemia (37%), fatigue (34%), and nausea (34%). Two patients died, but only 1 of the deaths was deemed treatment-related.

Dr Yu and colleagues ultimately concluded that the combination therapy of pembrolizumab plus olaparib is active in patients who previously received docetaxel and up to 2 hormone therapies of 2nd generation for mCRPC that is HRR wild type.

“Observed safety profile for the combination is consistent with individual profiles of pembro[lizumab] and olaparib,” they said.—Hina Khaliq

Yu EY, Massard C, Retz M, et al. Keynote-365 cohort a: Pembrolizumab (pembro) plus olaparib in docetaxelpretreated patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC). Presented at: the 2019 Genitourinary Cancers Symposium; February 14-16, 2019; San Francisco, CA. Abstract 145.