In an Australian phase IB to II study (PRINCE) reported in The Lancet Oncology, Sandhu et al found that the combination of lutetium-177–labeled PSMA-617 (LuPSMA-617) and pembrolizumab showed “encouraging” activity in patients with metastatic castration-resistant prostate cancer (mCRPC).
As stated by the investigators, “Preclinical evidence suggests radioligand therapy might induce immunogenic cell death that can be enhanced with [immune checkpoint inhibitors].”
Study Details
In the multicenter trial, 37 eligible patients enrolled between August 2019 and December 2020 received up to six cycles of LuPSMA-617 every 6 weeks with pembrolizumab at 200 mg every 3 weeks for up to 24 months. Patients had to have previous androgen receptor pathway inhibitor therapy and high prostate-specific membrane antigen (PSMA) expression; previous docetaxel was allowed. The primary efficacy measure was 50% prostate-specific antigen (PSA) response rate.
Key Findings
The median age of patients was 72 years, and 27 (73%) had received prior docetaxel. Patients received a median of 6 cycles of LuPSMA-617 and a median of 12 cycles of pembrolizumab.
Median follow-up was 30 months. A decrease of 50% or greater in PSA from baseline was observed in 28 patients (76%, 95% confidence interval [CI] = 59%–88%). A decrease of 90% or greater was observed in 17 patients (46%, 95% CI = 29%–63%). Among the 10 patients with measurable disease, 7 (70%, 95% CI = 35%–93%) had objective responses (all partial).
Median PSA-progression-free survival was 8.2 months (95% CI = 5.1–11.2 months), median radiographic progression-free survival was 11.2 months (95% CI = 5.1–14.1 months), and median overall survival was 20.8 months (95% CI = 13.5 months to not estimable).
Treatment-related grade 3 adverse events (no grade 4 or 5 events observed) occurred in 35% of patients, most commonly increased serum amylase, colitis, and fatigue (5% each). Grade 3 immune-related adverse events occurred in 30%, including the cases of increased serum amylase, colitis, and fatigue, as well as one case each of pancreatitis, pneumonitis, type 1 diabetes, nephritis, myasthenia gravis, and mucosal pemphigus.
The investigators concluded: “Multicycle [LuPSMA-617] and pembrolizumab showed encouraging activity with manageable toxicity that was consistent with [LuPSMA-617] or pembrolizumab, and the combination might provide durable clinical benefit in a subset of patients.”
Shahneen Sandhu, MBBS, of Peter MacCallum Cancer Centre, Melbourne, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by the Victorian Cancer Agency, Merck Sharp & Dohme, and Novartis. For full disclosures of the study authors, visit thelancet.com.
