Pembrolizumab Trial Results Contrast With Chemotherapy Alone in Metastatic Prostate Cancer
Patients receiving pembrolizumab combined with carboplatin and etoposide achieved an objective response rate of 28 percent, compared to 15 percent for chemotherapy alone, according to updated trial data presented at the ESMO Congress 2026. Gunhild von Amsberg of Hamburg, Germany, scheduled the presentation of the cohort I results from the Phase Ib/II KEYNOTE-365 trial, Oncodaily reported. The analysis included 70 patients with metastatic neuroendocrine prostate cancer to evaluate antitumour activity, survival outcomes, and safety.
Pembrolizumab Combination Trial Includes 70 Prostate Cancer Patients
Adults with centrally confirmed treatment-emergent or de novo metastatic neuroendocrine prostate cancer, including small-cell carcinoma, large-cell neuroendocrine carcinoma, or mixed histology, entered the study. Participants were randomized 1:1, a ratio later amended to 3:1. Patients could have received prior androgen deprivation therapy. At the November 19, 2025 data cutoff, investigators had randomized 70 patients to receive pembrolizumab plus chemotherapy (40 patients) or chemotherapy alone (30 patients). Most participants, specifically 73 percent, had treatment-emergent neuroendocrine prostate cancer, while 56 percent had a PD-L1 combined positive score of one or higher.
Response Rates and Survival Outcomes Compared
Among patients with measurable disease by RECIST v1.1 criteria, the objective response rate reached 28 percent with the pembrolizumab combination versus 15 percent with chemotherapy alone. Median duration of response measured 6.2 months for the combination group compared to 4.1 months for the control group. In the overall treatment population, median overall survival reached 10.2 months with pembrolizumab plus chemotherapy, contrasting with 7.1 months for chemotherapy alone, yielding a hazard ratio of 0.33. Subgroup analysis by PD-L1 status showed that among patients with a combined positive score of one or higher, the objective response rate was 40 percent versus 18 percent, and median overall survival reached 11.0 months compared to 4.8 months.
Combination Therapy Shows Lower Grade 3 to 5 Adverse Events
Treatment-related adverse events of any grade occurred in 95 percent of patients receiving pembrolizumab plus chemotherapy and 90 percent of those receiving chemotherapy alone. Grade 3 to 5 treatment-related adverse events affected 63 percent of the combination arm compared to 80 percent of the chemotherapy-alone arm. Adverse events led to treatment discontinuation in 8 percent of patients in the pembrolizumab group and 10 percent in the control group. No grade 5 treatment-related adverse events occurred with the combination therapy, while one grade 5 event, attributed to tumour lysis syndrome, occurred in the chemotherapy-alone group.
Frequently Asked Questions About KEYNOTE-365 Cohort I
What were the primary and secondary endpoints of KEYNOTE-365?
The trial assessed objective response rate by blinded independent central review using RECIST v1.1 and safety as primary endpoints. Secondary endpoints included duration of response, radiographic progression-free survival, and overall survival.
How many treatment cycles did participants receive?
Participants received four to six cycles of carboplatin and etoposide, with or without pembrolizumab administered every three weeks for up to 35 cycles.
Why must these findings be interpreted with caution?
The subgroup analyses involved small patient populations, particularly within the PD-L1 subsets, indicating that further analysis is planned before definitive conclusions can be drawn.
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