Loading
Adding pembrolizumab to enzalutamide did not help. The trial was stopped for futility, and three times as many men had a serious side effect.
KEYNOTE-641 randomised 1,244 men with chemotherapy-naive metastatic castration-resistant prostate cancer to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles, both with enzalutamide 160 mg daily.
At the data cutoff of 12 December 2022, median follow-up 27.6 months, neither primary endpoint was met. Median overall survival was 24.7 months with pembrolizumab against 27.3 months with placebo, hazard ratio 1.04 (95 percent confidence interval 0.88 to 1.22, p=0.66). Median radiographic progression-free survival was 10.4 against 9.0 months, hazard ratio 0.98 (0.84 to 1.14, p=0.41). The prespecified futility boundary for overall survival was crossed and the study was stopped.
The toxicity difference is the reason this is a harm and not merely a null result. Grade 3 or higher treatment-related adverse events occurred in 192 of 615 participants (31.2 percent) on pembrolizumab with enzalutamide against 67 of 620 (10.8 percent) on placebo with enzalutamide, and 71 (11.5 percent) against 21 (3.4 percent) discontinued for a treatment-related adverse event.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
1,244 randomised.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival (median)primary | Pembrolizumab with enzalutamide | 621 | 24.7 months | 1.04 (0.88 to 1.22) | 0.66 | link |
| Placebo with enzalutamide | 623 | 27.3 months | ||||
| Grade 3 or higher treatment-related adverse events | Pembrolizumab with enzalutamide | 615 | 31.2% | - | - | link |
| Placebo with enzalutamide | 620 | 10.8% |
Shares IMbassador250, KEYNOTE-921, Prostate cancer programmes that failed, and what each failure taught, Castration-resistant prostate cancer (CRPC).
Shares Androgen receptor pathway inhibitor (ARPI), Prostate cancer programmes that failed, and what each failure taught, Enzalutamide, Castration-resistant prostate cancer (CRPC).
Shares Androgen receptor pathway inhibitor (ARPI), Castration-resistant prostate cancer (CRPC), Androgen receptor, Metastatic castration-resistant prostate cancer.
Shares Androgen receptor pathway inhibitor (ARPI), Enzalutamide, Castration-resistant prostate cancer (CRPC), Androgen receptor.
Shares Enzalutamide, Metastatic castration-resistant prostate cancer, Merck & Co. (MSD), Pembrolizumab.
Shares Androgen receptor pathway inhibitor (ARPI), Prostate cancer programmes that failed, and what each failure taught, Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer.
Shares Androgen receptor pathway inhibitor (ARPI), Enzalutamide, Castration-resistant prostate cancer (CRPC), Androgen receptor.
Shares Androgen receptor pathway inhibitor (ARPI), Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer, Prostate cancer.