KEYNOTE-365 cohort A updated results: Pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

Abstract

100 Background: KEYNOTE-365 (NCT02861573) is a phase 1b/2 study evaluating pembro + other agents in mCRPC. Updated results from cohort A (pembro + olaparib) are reported. Methods: Docetaxel-pretreated, molecularly unselected pts with mCRPC with progression within 6 mo of screening per PSA or radiologic bone/soft tissue progression enrolled. Pts may have received 1 other chemotherapy and ≤2 2nd-generation hormone therapy (HT). Pts received pembro 200 mg IV Q3W + olaparib 400 mg PO BID. Primary end points: safety, PSA response rate (confirmed PSA decline ≥50%), and ORR per blinded independent central review. Results: Of 84 treated pts, 42 discontinued, primarily due to progression (n=29). Median age was 71 y (range, 47-83); 26% were PD-L1+, 26% had visceral disease, and 57% had RECIST-measurable disease. Median follow-up was 3 mo for all pts (n=81) and 14 mo for pts with ≥27 wks’ follow-up (n=41). See Table for efficacy outcomes. Treatment-related AEs occurred in 70 (83%) pts. Most frequent (≥30%) were nausea (33%) and anemia (31%). Grade 3-5 treatment-related AEs occurred in 29 (35%) pts. Three pts died of AEs (2 treatment related [l myocardial infarction, 1 unknown cause]). Conclusions: With additional follow-up, pembro + olaparib continued to show activity in docetaxel-pretreated, molecularly unselected pts who previously received HT for mCRPC. Safety of the combination was consistent with individual profiles of each agent. Clinical trial information: NCT02861573. [Table: see text]

Evolving Role of Immunotherapy in Metastatic Castration Refractory Prostate Cancer

“…The primary endpoints of this phase Ib/II trial are safety and PSA response rate, and secondary endpoints are ORR, OS, PFS, and time to PSA progression. Available results from 84 treated patients showed a PSA response rate of 9%, ORR of 8.3%, a median time to PSA progression of 16 weeks, median radiographic PFS of 4 months, and median OS of 14 months [42]. In a subgroup analysis, the T-cell-inflamed gene expression profile was not associated with ORR or PSA response [43].…”

“…Cohort A of KEYNOTE 365 is evaluating pembrolizumab in combination with olaparib in mCRPC patients previously treated with docetaxel and up to two novel hormonal therapies (NHTs) [42]. The primary endpoints of this phase Ib/II trial are safety and PSA response rate, and secondary endpoints are ORR, OS, PFS, and time to PSA progression.…”

Novel therapies are changing treatment paradigms in metastatic prostate cancer

“…The median rPFS and OS were 4 months (95% CI 3–8) and 14 months (95% CI 8–19), respectively. Any treatment-related AEs occurred in 70 (83%) patients, including most commonly nausea (33%) and anemia (31%), as well as grade 3–5 AEs in 29 (35%) patients [ 76 ].…”

Is There a Role for Immunotherapy in Prostate Cancer?

“…This study enrolled patients with mCRPC in three different cohorts: cohort A (84 patients) investigated the combination of pembrolizumab plus the poly ADP ribose polymerase inhibitor (PARPi) olaparib in molecularly unselected patients previously treated with docetaxel and second-generation hormone therapy; cohort B (104 patients) enrolled patients previously treated with abiraterone or enzalutamide to receive pembrolizumab plus docetaxel and prednisone; cohort C (102 patients) explored the combination of pembrolizumab plus enzalutamide in abiraterone-pretreated patients. In cohort A, PSA response rate was 9%, ORR was 8% (2/24 patients with RECIST measurable disease) with two partial responses, disease control rate was 22% [ 110 ]. Median radiographic PFS was 4.3 months and median OS was 14 months.…”