Efficacy and Safety of Cabazitaxel Versus Abiraterone or Enzalutamide in Older Patients with Metastatic Castration-resistant Prostate Cancer in the CARD Study.

In the CARD study (NCT02485691), cabazitaxel significantly improved median radiographic progression-free survival (rPFS) and overall survival (OS) versus abiraterone/enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously received docetaxel and progressed ≤12 mo on the alternative agent (abiraterone/enzalutamide).

To assess cabazitaxel versus abiraterone/enzalutamide in older (≥70 yr) and younger (<70 yr) patients in CARD.

Patients with mCRPC were randomized 1:1 to cabazitaxel (25 mg/m2 plus prednisone and granulocyte colony-stimulating factor) versus abiraterone (1000 mg plus prednisone) or enzalutamide (160 mg).

Analyses of rPFS (primary endpoint) and safety by age were prespecified; others were post hoc. Treatment groups were compared using stratified log-rank or Cochran-Mantel-Haenszel tests.

Of the 255 patients randomized, 135 were aged ≥70 yr (median 76 yr). Cabazitaxel, compared with abiraterone/enzalutamide, significantly improved median rPFS in older (8.2 vs 4.5 mo; hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.38-0.89; p = 0.012) and younger (7.4 vs 3.2 mo; HR = 0.47; 95% CI = 0.30-0.74; p < 0.001) patients. The median OS of cabazitaxel versus abiraterone/enzalutamide was 13.9 versus 9.4 mo in older patients (HR = 0.66; 95% CI = 0.41-1.06; p = 0.084), and it was 13.6 versus 11.8 mo in younger patients (HR = 0.66; 95% CI = 0.41-1.08; p = 0.093). Progression-free survival, prostate-specific antigen, and tumor and pain responses favored cabazitaxel, regardless of age. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 58% versus 49% of older patients receiving cabazitaxel versus abiraterone/enzalutamide and 48% versus 42% of younger patients. In older patients, cardiac adverse events were more frequent with abiraterone/enzalutamide; asthenia and diarrhea were more frequent with cabazitaxel.

Cabazitaxel improved efficacy outcomes versus abiraterone/enzalutamide in patients with mCRPC after prior docetaxel and abiraterone/enzalutamide, regardless of age. TEAEs were more frequent among older patients. The cabazitaxel safety profile was manageable across age groups.

Clinical trial data showed that cabazitaxel improved survival versus abiraterone/enzalutamide with manageable side effects in patients with metastatic castration-resistant prostate cancer who had previously received docetaxel and the alternative agent (abiraterone/enzalutamide), irrespective of age.

European urology. 2021 Jul 14 [Epub ahead of print]

Cora N Sternberg, Daniel Castellano, Johann de Bono, Karim Fizazi, Bertrand Tombal, Christian Wülfing, Gero Kramer, Jean-Christophe Eymard, Aristotelis Bamias, Joan Carles, Roberto Iacovelli, Bohuslav Melichar, Ásgerður Sverrisdóttir, Christine Theodore, Susan Feyerabend, Carole Helissey, Elizabeth M Poole, Ayse Ozatilgan, Christine Geffriaud-Ricouard, Ronald de Wit

Englander Institute for Precision Medicine, Weill Cornell Medicine, Meyer Cancer Center, New York, NY, USA. Electronic address: ., 12 de Octubre University Hospital, Madrid, Spain., The Institute of Cancer Research and the Royal Marsden Hospital, London, UK., Gustave Roussy Institute and University of Paris Saclay, Villejuif, France., Institute de Recherche Clinique, Université Catholique de Louvain, Brussels, Belgium., Department of Urology, Asklepios Tumorzentrum Hamburg, Asklepios Klinik Altona, Hamburg, Germany., Department of Urology, Medical University of Vienna, Vienna, Austria., Jean Godinot Institute, Reims, France., Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece., Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain., Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, Italy; Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy., Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic., Landspitali University Hospital, Reykjavik, Iceland., Foch Hospital, Suresnes, France., Studienpraxis Urologie, Nürtingen, Germany., Hôpital D'Instruction des Armées, Bégin, Saint Mandé, France., Sanofi, Global Medical Oncology, Cambridge, MA, USA., Sanofi, Europe Medical Oncology, Paris, France., Erasmus University Hospital, Rotterdam, The Netherlands.

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