The primary endpoint median radiographic (r) PFS was 8.9 months with cabazitaxel and 3,7 months with an ARSI (HR 0.54; 95% CI 0.40-0.73; p<0.001). The median OS was 13.6 months with cabazitaxel and 11.0 months with an ARSI ( HR for death 0.64; 95% CI 0.46-0.89; p =0.008). Therefore CARD produced irrefutable evidence that the taxane cabazitaxel is a superior treatment option as compared with cross-over between abiraterone and enzalutamide. There was no indication that the results with cross-over were any better in patients who were first treated with the ARSI before receiving docetaxel, meaning that AR sensitivity was not restored by giving one line of chemotherapy in-between. Similarly, there was no indication that the outcome was any better in patients receiving enzalutamide as the second ARSI ( after abiraterone). In post hoc analysis it was also investigated if the results were better in patients who had been treated for more than 12 months with the initial ARSI, but who fulfilled the entry criteria of CARD as they had demonstrated PSA progression within 12 months. REF1.
Therefore, cross-over between ARSI, irrespective of the sequence abi-enza or enza- abi and irrespective of the sequence ARSI- docetaxel-ARSI is inferior to treatment with cabazitaxel.
Since trial results do not always reflect those obtained in daily practice we collected “real-world” data from a huge database from patients from Europe, USA, Brazil, and Japan. Data from a total of 12,140 patients who had received at least one line of treatment for mCRPC, were analysed. A large proportion of patients had received 2 or more lines of ARSI, and 452 patients were identified who had received docetaxel, prior abi/enza, and cabazitaxel; defined as the CARD-like cohort. Patients in the CARD-like cohort had unfavorable characteristics vs CARD. More patients in the CARD-like cohort had received ARSI before docetaxel and had received the first ARSI for > 12 months. The cabazitaxel treatment duration, reflecting response duration, though, was identical, 21.9 weeks in the CARD-like cohort and 22 weeks in CARD. These results show that the CARD population is reflective of routine clinical practice and the duration of response to cabazitaxel is similar in a real-world population. These data confirm the robustness of the CARD study results, reflecting daily practice, and should alter the frequent sequential use of androgen—receptor-signaling inhibitor and result in the more effective treatment choice of cabazitaxel, as demonstrated by superior rPFS and OS.
Written by: Ronald de Wit, Stephen J Freedland, Stephane Oudard, Georgi Marinov, Philippe Capart, Austin J Combest, Ryan Peterson, Ayse Ozatilgan, Alicia K Morgans
Erasmus Medical Center, Rotterdam, The Netherlands., Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., George Pompidou European Hospital, University of Paris, Paris, France., PPD, Sofia, Bulgaria., Medimix, Miami, FL, USA., University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Sanofi, Global Medical Oncology, Cambridge, MA, USA., Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
References:
- de Wit R., Tombal B., Freedland S. "Use of Chemotherapy and Androgen Signaling–targeted Inhibitors in Patients with Metastatic Prostate Cancer." 2021. European Urology. 79, 2, 170-172, ISSN 0302-2838.
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