1. A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate CancerPhase Ib Trial of Atezo + Radium-223 in Pts with mCRPC
- Author
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Fong, Lawrence, Morris, Michael J, Sartor, Oliver, Higano, Celestia S, Pagliaro, Lance, Alva, Ajjai, Appleman, Leonard J, Tan, Winston, Vaishampayan, Ulka, Porcu, Raphaelle, Tayama, Darren, Kadel, Edward E, Yuen, Kobe C, Datye, Asim, Armstrong, Andrew J, and Petrylak, Daniel P
- Subjects
Cancer ,Clinical Research ,Urologic Diseases ,Clinical Trials and Supportive Activities ,Prostate Cancer ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Aged ,Aged ,80 and over ,Antibodies ,Monoclonal ,Humanized ,Combined Modality Therapy ,Double-Blind Method ,Humans ,Immune Checkpoint Inhibitors ,Male ,Middle Aged ,Neoplasm Metastasis ,Prostatic Neoplasms ,Castration-Resistant ,Radium ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeMen 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 methodsThis 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).ResultsAs 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).ConclusionsThis 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.
- Published
- 2021