Introduction and objective
The phase 1/2 KEYNOTE-365 study (NCT02861573) previously showed that pembro+olaparib was associated with antitumor activity and acceptable safety in molecularly unselected patients (pts) treated with docetaxel for mCRPC who were enrolled in cohort A. Updated results from cohort A are reported for all pts after a minimum of 11.4 months (mo) of follow-up.
Methods
Pts with molecularly unselected, docetaxel-pretreated mCRPC whose disease progressed within 6 mo of screening were enrolled. Pts received pembro 200 mg intravenously every 3 weeks + olaparib 400 mg capsule or 300 mg tablet orally twice daily. Primary end points: prostate-specific antigen (PSA) response rate (PSA decrease of ≥50% from baseline), objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR), and safety. Secondary end points: time to PSA progression, disease control rate (DCR), duration of response (DOR), radiographic progression-free survival (rPFS), and overall survival (OS).
Results
As of November 12, 2020, median follow-up (ie, time from enrollment to data cutoff) was 19.3 mo (range 11.4-45.9). Of 104 enrolled pts, 102 were treated; 92 pts discontinued treatment, primarily because of progressive disease (51.0%). Median age was 69.5 yrs (range 47-84), 28.4% of pts were PD-L1+, 33.3% had visceral disease, and 56.9% had measurable disease per BICR. Confirmed PSA response rate in all pts with a PSA measurement at baseline (N=102) was 14.7% (95% CI 8.5-23.1). Median (95% CI) time to PSA progression was 4.0 mo (3.0-4.9). In the 58 pts with measurable disease, confirmed ORR was 6.9% (1.9-16.7; 4 partial responses). Median DOR was not reached (range 7.2+ to 37.8+ mo); 2 pts had a response ≥12 mo. In all 102 treated pts, DCR was 26.5% (95% CI 18.2-36.1). Median (95% CI) rPFS was 5.2 mo (4.1-6.5) and median OS was 14.4 mo (10.4-17.9). Treatment-related adverse events (TRAEs) occurred in 93 pts (91.2%); most frequent (≥30%) were anemia (41.2%), nausea (41.2%), decreased appetite (30.4%), and fatigue (30.4%). Grade 3-5 TRAEs occurred in 49 pts (48.0%). Six pts (5.9%) died of AEs; 2 deaths were treatment related.
Conclusions
With additional follow-up, pembro+olaparib continued to show some antitumor activity in pts with molecularly unselected, docetaxel-pretreated mCRPC. Combination’s safety was consistent with that of each agent’s individual profile.