- Pembrolizumab showed ≥50% confirmed PSA decline in 17% of patients with heavily treated metastatic castrate-resistant prostate cancer (mCRPC).
- 75% of men who harbor pathogenic LRP1b mutations had ≥50% confirmed PSA decline.
Why this matters
- LRP1b mutations is a potential marker for pembrolizumab response in mCRPC.
- Study of 48 patients with heavily treated mCRPC who received ≥1 cycle of pembrolizumab.
- Funding: No external funding.
- 94% of patients received ≥3 prior treatment lines.
- 52% of patients received concurrent therapy with pembrolizumab.
- 21% of patients reported confirmed ≥30%, 17% had ≥50%, and 8% had confirmed ≥90% PSA decline.
- Of 23 patients who received concurrent enzalutamide, 22% reported ≥50% PSA decline.
- Median PSA-PFS was 1.8 months.
- In 38% of patients with evaluable somatic genomic profiling:
- Most common alterations: TMPRSS2-ERG fusion (33%), PTEN loss (28%), and AR amplifications (22%).
- 4 patients had LRP1b mutation, and 75% of these reported ≥50% PSA decline.
- Adverse event (AE) rate was 35%; 3 grade 3 AEs were reported.
- Retrospective design and small sample size.