Pembrolizumab with or without enzalutamide in selected populations of men with previously untreated metastatic castration-resistant prostate cancer harbouring programmed cell death ligand-1 staining: a retrospective study

BackgroundThe purpose of this retrospective study was to evaluate the survival outcomes of pembrolizumab (PEM) plus enzalutamide (ENZ) versus PEM alone in selected populations of men with previously untreated metastatic castration-resistant prostate cancer (mCRPC) harbouring programmed cell death ligand-1 (PD-L1) staining.MethodsConsecutive men with previously untreated mCRPC harbouring PD-L1 staining who underwent treatment with PEM plus ENZ (PE) or PEM alone (PA) at our medical centre from January 1, 2017, to January 31, 2021, were retrospectively identified. Follow-up was conducted monthly during the first year and then every 1month thereafter. The primary outcomes of the study were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were the frequency of key adverse events (AEs).ResultsIn total, 302 men were retrospectively reviewed, 96 of whom were deemed to be ineligible per the exclusion criteria, leaving 206 men (PE: n=100, median age 64years [range, 43-85] and PA: n=106, 65years [range, 45-82]) who were eligible for the study. The median follow-up for both groups was 34months (range, 2-42). At the final follow-up, the median OS was 25.1months (95% confidence interval [CI], 22.3-27.6) in the PE group versus 18.3months (95% CI, 16.5-20.9) in the PA group (hazard ratio [HR] 0.56; 95% CI, 0.39-0.80; p=0.001). A marked distinction was also observed in the median PFS (6.1months [95% CI, 4.7-7.8] for PE vs. 4.9months for PA (95% CI, 3.2-6.4) for PA; HR 0.55, 95% CI, 0.41-0.75; p= 0.001). There were noteworthy differences in the rate of the key AEs between the two groups (72.0% for PE vs. 45.3% for PA, p<0.001). Noteworthy differences were also detected for fatigue events (7.0% in the PE group vs. 0.9% in the PA group, p=0.025) and musculoskeletal events (9.0% for PE vs. 0.9% for PA, p=0.007), but these events tended to be manageable.ConclusionsAmong selected populations of men with previously untreated mCRPC harbouring PD-L1 staining, PEM added to ENZ treatment may significantly increase the survival benefits compared with PEM treatment alone regardless of tumor mutation status. The safety profile for PE plus ENZ tends to be manageable.

Automated summary

This retrospective study evaluated the survival outcomes of pembrolizumab (PEM) plus enzalutamide (ENZ) versus PEM alone in men with previously untreated metastatic castration-resistant prostate cancer (mCRPC) harbouring programmed cell death ligand-1 (PD-L1) staining. The study found that the combination treatment of PEM and ENZ significantly increased overall survival and progression-free survival compared to PEM alone, with a manageable safety profile.