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

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.

• Authors: 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 3rd, Kobe C Yuen, Asim Datye, Andrew J Armstrong, Daniel P Petrylak
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 27 Issue 17 Pg. 4746-4756 (09 01 2021) ISSN: 1557-3265 [Electronic] United States
• PMID: 34108181 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: ©2021 The Authors; Published by the American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal, Humanized
• Immune Checkpoint Inhibitors
• atezolizumab
• Radium-223
• Radium

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Combined Modality Therapy
• Double-Blind Method
• Humans
• Immune Checkpoint Inhibitors (therapeutic use)
• Male
• Middle Aged
• Neoplasm Metastasis
• Prostatic Neoplasms, Castration-Resistant (drug therapy, pathology, radiotherapy)
• Radium (therapeutic use)