A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer
Open Access
- 9 June 2021
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 27 (17), 4746-4756
- https://doi.org/10.1158/1078-0432.ccr-21-0063
Abstract
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. 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). 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). 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.Keywords
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Funding Information
- Roche (n/a)
This publication has 42 references indexed in Scilit:
- Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in miceJCI Insight, 2014
- Activity of Cabazitaxel in Castration-resistant Prostate Cancer Progressing After Docetaxel and Next-generation Endocrine AgentsEuropean Urology, 2013
- Alpha Emitter Radium-223 and Survival in Metastatic Prostate CancerThe New England Journal of Medicine, 2013
- Bone-targeting radiopharmaceuticals for the treatment of prostate cancer with bone metastasesCancer Letters, 2012
- Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in CancerThe New England Journal of Medicine, 2012
- The Abscopal Effect Associated With a Systemic Anti-melanoma Immune ResponseInternational Journal of Radiation Oncology*Biology*Physics, 2012
- From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancerThe Journal of Pathology, 2012
- Immunologic Correlates of the Abscopal Effect in a Patient with MelanomaThe New England Journal of Medicine, 2012
- Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response CriteriaClinical Cancer Research, 2009
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal of Cancer, 2009