A phase Ib study of atezolizumab with radium-223 dichloride in men with metastatic castration-resistant prostate cancer

Lawrence Fong, Michael J. Morris, Oliver Sartor, Celestia S. Higano, Lance Pagliaro, Ajjai Alva, Leonard J. Appleman, Winston Tan, Ulka Vaishampayan, Raphaelle Porcu, Darren Tayama, Edward E. Kadel, Kobe C. Yuen, Asim Datye, Andrew J. Armstrong, Daniel P. Petrylak

Research output: Contribution to journalArticlepeer-review

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 (radium-223) in men with mCRPC. Patients and Methods: 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), PSA responses, and overall survival (OS). Results: As of October 4, 2019, 44 of 45 men were evaluable. All 44 had ≥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% confidence interval (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.

Original languageEnglish (US)
Pages (from-to)4746-4756
Number of pages11
JournalClinical Cancer Research
Volume27
Issue number17
DOIs
StatePublished - Sep 1 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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