Pembrolizumab Plus Docetaxel and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort B Study

Eur Urol. 2022 Jul;82(1):22-30. doi: 10.1016/j.eururo.2022.02.023. Epub 2022 Apr 6.


Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) frequently receive docetaxel after they develop resistance to abiraterone or enzalutamide and need more efficacious treatments.

Objective: To evaluate the efficacy and safety of pembrolizumab plus docetaxel and prednisone in patients with mCRPC.

Design, setting, and participants: The trial included patients with mCRPC in the phase 1b/2 KEYNOTE-365 cohort B study who were chemotherapy naïve and who experienced failure of or were intolerant to ≥4 wk of abiraterone or enzalutamide for mCRPC with progressive disease within 6 mo of screening.

Intervention: Pembrolizumab 200 mg intravenously (IV) every 3 wk (Q3W), docetaxel 75 mg/m2 IV Q3W, and prednisone 5 mg orally twice daily.

Outcome measurements and statistical analysis: The primary endpoints were safety, the prostate-specific antigen (PSA) response rate, and the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary endpoints included time to PSA progression; the disease control rate (DCR) and duration of response (DOR) according to RECIST v1.1 by BICR; ORR, DCR, DOR, and radiographic progression-free survival (rPFS) according to Prostate Cancer Working Group 3-modified RECIST v1.1 by BICR; and overall survival (OS).

Results and limitations: Among 104 treated patients, 52 had measurable disease. The median time from allocation to data cutoff (July 9, 2020) was 32.4 mo, during which 101 patients discontinued treatment, 81 (78%) for disease progression. The confirmed PSA response rate was 34% and the confirmed ORR (RECIST v1.1) was 23%. Median rPFS and OS were 8.5 mo and 20.2 mo, respectively. Treatment-related adverse events (TRAEs) occurred in 100 patients (96%). Grade 3-5 TRAEs occurred in 46 patients (44%). Seven AE-related deaths (6.7%) occurred (2 due to treatment-related pneumonitis). Limitations of the study include the single-arm design and small sample size.

Conclusions: Pembrolizumab plus docetaxel and prednisone demonstrated antitumor activity in chemotherapy-naïve patients with mCRPC treated with abiraterone or enzalutamide for mCRPC. Safety was consistent with profiles for the individual agents. Further investigation is warranted.

Patient summary: We evaluated the efficacy and safety of the anti-PD-1 antibody pembrolizumab combined with the chemotherapy drug docetaxel and the steroid prednisone for patients with metastatic prostate cancer resistant to androgen deprivation therapy , and who never received chemotherapy. The combination showed antitumor activity and manageable safety in this patient population. This trial is registered on as NCT02861573.

Keywords: Docetaxel; Metastatic castration-resistant prostate cancer; Pembrolizumab; Prednisone.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abiraterone Acetate
  • Androgen Antagonists / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Disease-Free Survival
  • Docetaxel / therapeutic use
  • Humans
  • Male
  • Prednisone / therapeutic use
  • Prostate-Specific Antigen
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / pathology
  • Treatment Outcome


  • Androgen Antagonists
  • Antibodies, Monoclonal, Humanized
  • Docetaxel
  • pembrolizumab
  • Prostate-Specific Antigen
  • Abiraterone Acetate
  • Prednisone

Associated data