TY - JOUR
T1 - A phase Ib study of atezolizumab with radium-223 dichloride in men with metastatic castration-resistant prostate cancer
AU - Fong, Lawrence
AU - Morris, Michael J.
AU - Sartor, Oliver
AU - Higano, Celestia S.
AU - Pagliaro, Lance
AU - Alva, Ajjai
AU - Appleman, Leonard J.
AU - Tan, Winston
AU - Vaishampayan, Ulka
AU - Porcu, Raphaelle
AU - Tayama, Darren
AU - Kadel, Edward E.
AU - Yuen, Kobe C.
AU - Datye, Asim
AU - Armstrong, Andrew J.
AU - Petrylak, Daniel P.
N1 - Funding Information:
This study was sponsored by F. Hoffmann-La Roche Ltd/Genentech, Inc, a member of the Roche Group. We thank the patients participating in this trial and their families, the nurses, research coordinators, data managers, and clinical study site investigators. Medical writing assistance for this article was provided by Priscilla Hong, PharmD, of Health Interactions, Inc, and funded by F. Hoffmann-La Roche, Ltd.
Funding Information:
This study was sponsored by F. Hoffmann-La Roche Ltd/Genentech, Inc, a member of the Roche Group. We thank the patients participating in this trial and their families, the nurses, research coordinators, data managers, and clinical
Publisher Copyright:
© 2021 American Association for Cancer Research.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-21-0063
DO - 10.1158/1078-0432.CCR-21-0063
M3 - Article
C2 - 34108181
AN - SCOPUS:85114158874
VL - 27
SP - 4746
EP - 4756
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 17
ER -