Docetaxel has been a standard treatment for metastatic castration-resistant prostate cancer (mCRPC) since 2004. Cabazitaxel, a related taxane, was approved in 2010 for patients with mCRPC who had been previously treated with docetaxel. The comparative effectiveness of docetaxel rechallenge vs switching to cabazitaxel after prior docetaxel for mCRPC remains unclear.
To compare the clinical outcomes associated with docetaxel rechallenge vs cabazitaxel in patients with mCRPC who did not experience disease progression during prior administration of docetaxel in the mCRPC setting.
This retrospective cohort study was conducted in the nationwide Veterans Affairs health care system, using inverse probability of treatment weighting to control for potential confounders. Patients who were diagnosed with chemonaive mCRPC between January 1, 2010, and December 31, 2023, received initial docetaxel treatment, and did not experience disease progression were eligible to participate.
Treatment with docetaxel rechallenge or cabazitaxel.
The primary outcome was overall survival (OS) from the initiation of the second course of taxane, which was compared in patients treated with docetaxel rechallenge vs cabazitaxel using weighted Kaplan-Meier analysis and Cox proportional hazards regression models. Secondary outcomes included prostate-specific antigen response, time to next systemic treatment or death, and subsequent treatments received.
A total of 669 patients (407 receiving cabazitaxel and 262 receiving docetaxel rechallenge) with a median age of 72 (IQR, 67-77) years were included. Patients treated with docetaxel rechallenge had a significantly longer OS (median, 12.3 [IQR, 10.5-13.8] months) compared with those treated with cabazitaxel (median, 9.6 [IQR, 8.6-11.1] months), with a hazard ratio of 0.81 (95% CI, 0.55-0.99; P = .04). Descriptive analysis of secondary outcomes was consistent with this finding, including prostate-specific antigen response (weighted 9.8% achieving reduction of 90% or more in the docetaxel rechallenge group vs 3.0% in the cabazitaxel group) and time to next treatment or death (median, 10.7 [IQR, 7.8-12.7] months in the docetaxel rechallenge group vs 8.9 [IQR, 7.1-10.5 months] in the cabazitaxel group). Use of platinum, immunotherapy, or poly (ADP-ribose) polymerase inhibitors was similar between patients treated with cabazitaxel and docetaxel rechallenge.
In this cohort study of patients with mCRPC, docetaxel rechallenge was associated with improved OS compared with cabazitaxel among patients who did not experience disease progression during prior docetaxel for mCRPC. These findings support docetaxel rechallenge as a treatment option for patients in this scenario.
JAMA network open. 2026 Jan 02*** epublish ***
Pedro C Barata, June K Corrigan, Jennifer La, John M Culnan, Elliot Akama-Garren, Karlynn N Dulberger, Clark Dumontier, Jason Hansen, John R Bihn, Rhonda L Bitting, Mary T Brophy, Heather H Cheng, Matthew R Cooperberg, Nhan V Do, Tanya Dorff, Antonio Tito Fojo, J Michael Gaziano, Sergey D Goryachev, Susan Halabi, Richard L Hauger, David M Nanus, Timothy R Rebbeck, Chong-Xian Pan, Martin W Schoen, Kaitlin N Swinnerton, Kenute Myrie, Rachel B Ramoni, Nathanael R Fillmore, Channing J Paller, Matthew B Rettig
Division of Solid Tumor Oncology, Department of Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio., Massachusetts Veterans Epidemiology Research and Information Center, Department of Veterans Affairs Healthcare System, Boston., Department of Medicine, Harvard Medical School, Boston, Massachusetts., College of Osteopathic Medicine, University of New England, Biddeford, Maine., Durham Veterans Affairs (VA) Medical Center, Durham, North Carolina., Division of Oncology, Department of Medicine, University of Washington, Seattle., Surgical Service, San Francisco VA Medical Center (VAMC), San Francisco, California., Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California., Herbert Irving Comprehensive Cancer Center, Columbia University and James J. Peters VAMC, Bronx, New York., Department of Medicine, Duke University School of Medicine, Durham, North Carolina., Research Service, Department of Veterans Affairs San Diego Healthcare System, San Diego, California., Department of Medicine, Weill Cornell Medicine, New York, New York., Harvard T. H. Chan School of Public Health, Cambridge, Massachusetts., John J. Cohran Veterans Hospital, VA St Louis Healthcare System, St Louis, Missouri., Office of Research and Development, Veterans Health Administration, US Department of Veterans Affairs, Washington, DC., Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Division of Hematology-Oncology, Greater Los Angeles Veterans Affairs Medical Center, Los Angeles, California.