A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer

This article was originally published here

Clin Cancer Res. 2021 Jun 9:clincanres.0063.2021. doi: 10.1158/1078-0432.CCR-21-0063. Online ahead of print.

ABSTRACT

PURPOSE: Men with metastatic castration-resistant prostate cancer (mCRPC) have limited treatment options after progressing on hormonal therapy and chemotherapy. Here, we evaluate the safety and efficacy of atezolizumab (anti-PD-L1) + radium-223 dichloride in men with mCRPC.

EXPERIMENTAL DESIGN: This phase Ib study evaluated atezolizumab + radium-223 in men with mCRPC and bone and lymph node and/or visceral metastases that progressed after androgen pathway inhibitor treatment. Following safety assessment of concurrent dosing, 45 men were randomized 1:1:1 to concurrent or one of two staggered dosing schedules with either agent introduced one cycle before the other. This was followed by a safety-efficacy expansion cohort (randomized 1:1:1). The primary endpoints were safety and objective response rate (ORR) by RECIST 1.1. Secondary endpoints included radiographic progression-free survival (rPFS), prostate-specific antigen (PSA) responses and overall survival (OS).

RESULTS: As of October 4, 2019, 44 of 45 men were evaluable. All 44 had {greater than or equal to}1 all-cause adverse event (AE); 23 (52.3%) had a grade 3/4 AE. Fifteen (34.1%) grade 3/4 and 3 (6.8%) grade 5 AEs were related to atezolizumab; none were related to radium-223. Confirmed ORR was 6.8% (95% CI: 1.4-18.7), median rPFS was 3.0 months (95% CI: 2.8-4.6), median PSA progression was 3.0 months (95% CI: 2.8-3.3) and median OS was 16.3 months (95% CI: 10.9-22.3).

CONCLUSIONS: This phase Ib study demonstrated that atezolizumab+radium-223, regardless of administration schedule, had greater toxicity than either drug alone, with no clear evidence of additional clinical benefit for patients with mCRPC and bone and lymph node and/or visceral metastases.

PMID:34108181 | DOI:10.1158/1078-0432.CCR-21-0063