Pembrolizumab (Pembro) plus enzalutamide (Enz) in metastatic castration resistant prostate cancer (mCRPC): Extended follow up.

Abstract

5047 Background: Anti-PD1 treatment with Pembro is a promising treatment strategy in many solid tumors. Here, we report clinical outcomes of adding Pembro to men with mCRPC progressing on Enz. Methods: We enrolled 28 patients with mCRPC who had not previously had chemotherapy for mCRPC or checkpoint inhibitors. Pembro was given 200 mg IV every 3 weeks for 4 doses, which could be repeated for the patients who had stable or responsive disease. The primary endpoint was prostate specific antigen (PSA) response (PSA decline of ≥ 50%). Secondary endpoints were radiographic objective response (RECIST 1.1), PSA progression free survival, time to subsequent treatment, and time to death from any cause. Baseline tumor biopsies were done if there was a metastatic deposit amenable to biopsy. We are presenting updated clinical outcomes and evaluation of samples for presence of Program Death-Ligand 1 (PD-L1), microsatellite instability (MSI) and DNA repair defects. Results: Five of 28 patients (18%) had a PSA decline of ≥ 50%. Three of 12 patients (25%) with measurable disease at baseline achieved an objective response on radiographs. Of the responders (R), one passed away from an unrelated cause without PSA recurrence after 14.2 mos, and one relapsed after 10 mos and did not respond to a second course of Pembro. The other 3 continue to be in response (range 21.9-33.8 mos). For the entire cohort, the median follow up was 22.7 mos, and the median PSA-PFS time was 3.8 mos (95% CI: 2.8 – 9.9 mos). Time to subsequent treatment was 8.2 mos (95% CI: 5.1 – 12.8 mos). Median overall survival was 22.2 mos (95% CI: 14.7 – 28 .4 mos). Median radiographic PFS was 10.8 mos (5-22 mos). There were 8 immune related adverse events in 7 unique patients (hypothyroid 3, hyperthyroid 1, myositis 2, colitis 2). Seventeen patients had baseline biopsies of a metastatic deposit: 3 R, 14 non-responders (NR). Of the 3 R who had baseline biopsies, one had MSI and DNA repair defects. The other 2 had neither. Of the NR who had sequencing, 4 had a DNA repair defects, and none had MSI. None of the biopsies showed tumoral PD-L1 expression (Qualtek, 22C3). Conclusions: Pembro has activity in mCRPC when added to Enz. Responses were deep and durable in a subset of patients. Clinical trial information: NCT02312557.