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Pembrolizumab Combinations Show Promise in mCRPC

All of the pembrolizumab regimens were safe in patients with metastatic castration-resistant prostate cancer
21 Nov 2020
Cytotoxic Therapy;  Immunotherapy;  Targeted Therapy;  Endocrine Therapy
Prostate Cancer

Three individual combination treatments containing pembrolizumab provided anti-tumour activity in patients with metastatic castration-resistant prostate cancer (mCRPC), according to updated data from the KEYNOTE-365 study reported at the ESMO Asia Virtual Congress 2020, held from 20 to 22 November 2020.

Professor Anthony M. Joshua of the Kinghorn Cancer Centre, St Vincent’s Hospital in Sydney, NSW, Australia presented updated findings from cohorts A, B, and C of the multicohort, open-label phase Ib/II KEYNOTE-365 (NCT02861573) study.

The KEYNOTE-365 investigators assessed the safety and efficacy of pembrolizumab combination treatment in 3 cohorts of patients classified according to pretreatment. This non-randomised study administered pembrolizumab at 200 mg IV every 3 weeks to patients in 3 cohorts. Patients pretreated with docetaxel (cohort A) received olaparib as a 400 mg capsule or 300 mg tablet twice daily (n = 84). In cohort B, in addition to pembrolizumab, docetaxel at 75 mg/m2 IV every 3 weeks plus oral prednisone at 5 mg twice daily was administered to patients pretreated with either abiraterone acetate or enzalutamide (n = 104). In cohort C, in addition to pembrolizumab, oral enzalutamide at 160 mg/day was administered to patients pretreated with abiraterone acetate (n = 102).

Pembrolizumab-Combinations-Show-Promise-in-mCRPC

KEYNOTE-365 study design.

© Anthony M. Joshua.

The primary endpoints were prostate specific antigen (PSA) response rate, defined as confirmed PSA decrease ≥50%, objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR), and safety.

PSA response was obseverd in 9% of cohort A, 28% cohort B, and 22% of patients in cohort C.

Measurable disease was observed in 48 (57%; cohort A), 52 (50%; cohort B), and 40 (39%; cohort C) patients in the total population of each cohort. In patients with measurable disease and ≥27 weeks of follow-up, the ORR was 8% (2/24) in cohort A, 18% (7/39) in cohort B, and 12% (3/25) in cohort C; the best responses were 2 partial response (PR), 7 PR, and 2 complete response plus 1 PR in cohorts A, B, and C, respectively,

Median radiographic progression-free survival (rPFS) was 4.3 months (95% confidence interval [CI] 3.4-7.7; cohort A), 8.3 months (95% CI 7.6-10.1; cohort B), and 6.1 months (95% CI 4.4-6.5; cohort C); 12-month rPFS rates were 23.3%, 24.0%, and 24.6%, respectively.

Median overall survival (OS) in the respective cohorts was 14.4 months (95% CI 8.1-18.5), 20.4 months (95% CI 16.9-not reached [NR]), and 20.4 months (95% CI 15.5-NR); 12-month OS rates in the respective cohorts were 58.2%, 75.8%, and 72.8%.

Grade ≥3 treatment-related adverse events (TRAEs) occurred in 35%, 40%, and 39% of patients in cohorts A, B, and C, respectively.

Deaths due to TRAEs occurred in 2 cohort A patients (1 myocardial infarction, 1 cause unknown), 2 in cohort B (pneumonitis), and 1 patient in cohort C (cause unknown).

Conclusions

Based on these findings, the investigators concluded that all three pembrolizumab combinations demonstrated anti-tumor activity in mCRPC, and also showed a tolerability profile that was consistent with the individual profiles of each agent.

They noted that phase III studies of each of these combinations are ongoing.

KEYNOTE-365 was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. 

Reference

217O – Joshua AM, Gurney H, Retz M, et al. Pembrolizumab (pembro) Combination Therapies in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC): Cohorts A-C of the Phase 1b/2 KEYNOTE-365 Study. ESMO Asia Virtual Congress 2020 (20-22 November).

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