Final Analysis of the Ipilimumab Versus Placebo Following Radiotherapy Phase III Trial in Postdocetaxel Metastatic Castration-resistant Prostate Cancer Identifies an Excess of Long-term Survivors
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Background The phase 3 trial CA184-043 evaluated radiotherapy to bone metastases followed by Ipilimumab or placebo in men with metastatic castrate-resistant prostate cancer (mCRPC) who had received docetaxel previously. In a prior analysis, the trial's primary endpoint (overall survival [OS]) was not improved significantly.Objective To report the final analysis of OS.Design, setting, and participants A total of 799 patients were randomized to receive a single dose of radiotherapy to one or more bone metastases followed by either Ipilimumab (n = 399) or placebo (n = 400).Outcome measurements and statistical analysis OS was analyzed in the intention-to-treat population. Prespecified and exploratory subset analyses based on Kaplan-Meier/Cox methodology were performed.Results and limitations During an additional follow-up of approximately 2.4 yr since the primary analysis, 721/799 patients have died. Survival analysis showed crossing of the curves at 7-8 mo, followed by persistent separation of the curves beyond that point, favoring the ipilimumab arm. Given the lack of proportional hazards, a piecewise hazard model showed that the hazard ratio (HR) changed over time: the HR was 1.49 (95% confidence interval 1.12, 1.99) for 0-5 mo, 0.66 (0.51, 0.86) for 5-12 mo, and 0.66 (0.52, 0.84) beyond 12 mo. OS rates were higher in the ipilimumab versus placebo arms at 2 yr (25.2% vs 16.6%), 3 yr (15.3% vs 7.9%), 4 yr (10.1% vs 3.3%), and 5 yr (7.9% vs. 2.7%). Disease progression was the most frequent cause of death in both arms. In seven patients (1.8%) in the ipilimumab arm and one (0.3%) in the placebo arm, the primary cause of death was reported as study drug toxicity. No long-term safety signals were identified.Conclusions In this preplanned long-term analysis, OS favored ipilimumab plus radiotherapy versus placebo plus radiotherapy for patients with postdocetaxel mCRPC. OS rates at 3, 4, and 5 yr were approximately two to three times higher in the ipilimumab arm.Patient summary After longer follow-up, survival favored the group of men who received ipilimumab, with overall survival rates being two to three times higher at 3 yr and beyond.
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A phase III trial of anti-CTLA4 plus radiotherapy in metastatic prostate cancer failed to meet its primary endpoint.
“Similarly, a phase III combination study of anti-CTLA4 plus radiotherapy in patients with metastatic prostate cancer also failed to meet its primary endpoint (100, 107).”
From The Next Decade of Immune Checkpoint Therapy (2021) · cites this paper as [107]
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The Next Decade of Immune Checkpoint Therapy
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- Authors
- Fizazi, K., Drake, C. G., Beer, T. M., Kwon, E. D., Scher, H. I., Gerritsen, W. R., Bossi, A., den Eertwegh, A. J. M. V., Krainer, M., Houede, N., Santos, R., Mahammedi, H., Ng, S., Danielli, R., Franke, F. A., Sundar, S., Agarwal, N., Bergman, A. M., Ciuleanu, T. E., Korbenfeld, E., Sengeløv, L., Hansen, S., McHenry, M. B., Chen, A., & Logothetis, C.
- Affiliations
- Université Paris-Sud (FR)
- Herbert Irving Comprehensive Cancer Center (US)
- OHSU Knight Cancer Institute (US)
- Mayo Clinic (US)
- Memorial Sloan Kettering Cancer Center (US)
- Radboud University Medical Center (NL)
- Institut Gustave Roussy (FR)
- Vienna General Hospital (AT)
- Centre Jean Perrin (FR)
- St John of God Subiaco Hospital (AU)
- University of Siena (IT)
- Hospital São José do Avaí (BR)
- Nottingham University Hospitals NHS Trust (GB)
- Huntsman Cancer Institute (US)
- Institute of Oncology Prof. Dr. Ion Chiricuta (RO)
- Hospital Británico de Buenos Aires (AR)
- Herlev Hospital (DK)
- Bristol-Myers Squibb (United States) (US)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Fizazi, Karim
- ORCID
- Venue
- European Urology
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 78
- Issue
- 6
- Pages
- 822-830
- ISSN
- 0302-2838 (ISSN-L)
- PMC
- PMC8428575
- OpenAlex
- W3049720236
- Cited by
- 185
- References
- 41
- Citations by year
- 2026: 22 · 2025: 31 · 2024: 27 · 2023: 27 · 2022: 37 · 2021: 32 · 2020: 9
- FWCI
- 14.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- European Urology (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Bristol-Myers Squibb
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- metastatic castration-resistant prostate cancer, docetaxel, overall survival, long-term survival, immune checkpoint inhibitors, disease progression, treatment toxicity, prognostic factors, prognostic score
- MeSH terms
- Antineoplastic Agents, Immunological, Ipilimumab, Docetaxel, Aged, Antineoplastic Agents, Bone Neoplasms, Combined Modality Therapy, Double-Blind Method, Humans, Male, Middle Aged, Time Factors, Survival Rate, Prostatic Neoplasms, Castration-Resistant
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