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Combination therapy with pembrolizumab, docetaxel and prednisone for previously treated metastatic, castration-resistant prostate cancer

The phase Ib/II KEYNOTE-365 trial is currently investigating different pembrolizumab-based treatment regimens in patients with metastatic castration-resistant prostate cancer (mCRPC). Updated results of cohort B were presented at ASCO GU 2021 confirm the anti-tumour activity of pembrolizumab plus docetaxel and prednisone, with a confirmed PSA response in a third of patients and a median overall survival (OS) of 20.2 months in mCRPC patients who were pre-treated with abiraterone or enzalutamide.


The phase Ib/II KEYNOTE-365 trial is assessing the efficacy of pembrolizumab in combination with 4 different study medications across 4 cohorts. In cohort B of this study, the combination of pembrolizumab with docetaxel and prednisone is being evaluated in mCRPC patients who previously received abiraterone or enzalutamide. In this cohort, a total of 104 mCRPC patients were treated with pembrolizumab PEMBRO (200 mg every 3 weeks), plus docetaxel (75 mg/m2 every 3 weeks) and prednisone (5 mg twice daily). Participants were required to have failed on, or be intolerant of either abiraterone or enzalutamide in a pre-chemotherapy mCRPC setting. Primary endpoints of this study included objective response rate (ORR), PSA response rate and safety. Secondary study objectives included disease control rate (DCR), radiographic progression-free survival (rPFS) and overall survival (OS).

≥50% PSA decrease in a third of patients

In this cohort, the median age was 68 years of age, with 74% of patients being at least 65 years. A quarter of patients had visceral disease and 23.1% were PD-L1-positive. With an additional 1 year of follow-up, a confirmed PSA response of 34.0% was reported, defined as a ≥50% PSA reduction from baseline. Overall, 73.8% of patients experienced some form of PSA decrease from baseline. For patients with measurable disease, the ORR was found to be 23.1%, with a DCR of 73.1%. Among patients with measurable disease at baseline, 90.4% obtained a reduction in tumour size from baseline, with 42.3% of patients having a tumour decrease of ≥30%. The median rPFS was reported at 8.5 months with 76.9% and 26.2% of patients being free of radiographic disease progression at 6 and 12 months, respectively. The median OS in this cohort mounted to 20.2 months, with 75.9% of patients being alive at the 12-month landmark.

The safety profile observed in this cohort was comparable to the known safety profile of each individual treatment. The most common grade ≥3 treatment-related adverse events (AEs) were diarrhoea (2.9%) and fatigue (2.9%). The most common grade ≥3 immune-mediated AEs were pneumonitis and colitis (both 3.8%). Overall, 2 patients died due to treatment-related pneumonitis.


The combination of pembrolizumab plus docetaxel and prednisone continues to show promising anti-tumour activity, with a confirmed PSA response rate of 34% and an ORR of 23.1%. The safety profile of cohort B was manageable, and comparable to the known safety profiles of each individual agent. The long median rPFS and OS data obtained in this cohort further supports the ongoing phase III investigation of this therapeutic combination in mCRPC patients who have previously been treated with enzalutamide or abiraterone (Keynote-921).


Appleman LJ et al., KEYNOTE-365 cohort B: Pembrolizumab (pembro) plus docetaxel and prednisone in abiraterone (abi) or enzalutamide (enza)- pretreated patients with metastatic castration-resistant prostate cancer (mCRPC)- New data after an additional 1 year of follow-up. Presented at ASCO GU 2021; Abstract 10.

Speaker Leonard Joseph Appleman

Leonard Joseph Appleman

Leonard Joseph Appleman, MD, PhD, University of Pittsburgh, Pittsburgh, United States


See: Keyslides

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