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.
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).
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).
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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021 Jun 09 [Epub ahead of print]
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
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco ., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College., Medicine and Urology, Tulane University School of Medicine., University of Washington., Oncology, Mayo Clinic., Internal Medicine, Division of Hematology/Oncology, University of Michigan–Ann Arbor., Division of Hematology-Oncology, University of Pittsburgh., Hematology and Oncology, Mayo Clinic Jacksonville., Department of Medicine, University of Michigan Medical School., Product Development Oncology, F. Hoffmann-La Roche, Ltd., Genentech., Oncology Biomarker Development, Genentech, Inc., Oncology Biomarker Development, Genentech., Divisions of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke Cancer Institute., Prostate and Urologic Cancers Program, Yale Cancer Center.