Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer.
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Date
2019-12-26ICR Author
Author
de Wit, R
de Bono, J
Sternberg, CN
Fizazi, K
Tombal, B
Wülfing, C
Kramer, G
Eymard, J-C
Bamias, A
Carles, J
Iacovelli, R
Melichar, B
Sverrisdóttir, Á
Theodore, C
Feyerabend, S
Helissey, C
Ozatilgan, A
Geffriaud-Ricouard, C
Castellano, D
CARD Investigators,
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: The efficacy and safety of cabazitaxel, as compared with an androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who were previously treated with docetaxel and had progression within 12 months while receiving the alternative inhibitor (abiraterone or enzalutamide) are unclear. METHODS: We randomly assigned, in a 1:1 ratio, patients who had previously received docetaxel and an androgen-signaling-targeted inhibitor (abiraterone or enzalutamide) to receive cabazitaxel (at a dose of 25 mg per square meter of body-surface area intravenously every 3 weeks, plus prednisone daily and granulocyte colony-stimulating factor) or the other androgen-signaling-targeted inhibitor (either 1000 mg of abiraterone plus prednisone daily or 160 mg of enzalutamide daily). The primary end point was imaging-based progression-free survival. Secondary end points of survival, response, and safety were assessed. RESULTS: A total of 255 patients underwent randomization. After a median follow-up of 9.2 months, imaging-based progression or death was reported in 95 of 129 patients (73.6%) in the cabazitaxel group, as compared with 101 of 126 patients (80.2%) in the group that received an androgen-signaling-targeted inhibitor (hazard ratio, 0.54; 95% confidence interval [CI], 0.40 to 0.73; P<0.001). The median imaging-based progression-free survival was 8.0 months with cabazitaxel and 3.7 months with the androgen-signaling-targeted inhibitor. The median overall survival was 13.6 months with cabazitaxel and 11.0 months with the androgen-signaling-targeted inhibitor (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.89; P = 0.008). The median progression-free survival was 4.4 months with cabazitaxel and 2.7 months with an androgen-signaling-targeted inhibitor (hazard ratio for progression or death, 0.52; 95% CI, 0.40 to 0.68; P<0.001), a prostate-specific antigen response occurred in 35.7% and 13.5% of the patients, respectively (P<0.001), and tumor response was noted in 36.5% and 11.5% (P = 0.004). Adverse events of grade 3 or higher occurred in 56.3% of patients receiving cabazitaxel and in 52.4% of those receiving an androgen-signaling-targeted inhibitor. No new safety signals were observed. CONCLUSIONS: Cabazitaxel significantly improved a number of clinical outcomes, as compared with the androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who had been previously treated with docetaxel and the alternative androgen-signaling-targeted agent (abiraterone or enzalutamide). (Funded by Sanofi; CARD ClinicalTrials.gov number, NCT02485691.).
Collections
Subject
CARD Investigators
Humans
Taxoids
Phenylthiohydantoin
Androstenes
Prednisone
Androgen Antagonists
Antineoplastic Combined Chemotherapy Protocols
Infusions, Intravenous
Aged
Aged, 80 and over
Middle Aged
Male
Kaplan-Meier Estimate
Prostatic Neoplasms, Castration-Resistant
Progression-Free Survival
Research team
Prostate Cancer Targeted Therapy Group
Language
eng
License start date
2019-12
Citation
The New England journal of medicine, 2019, 381 (26), pp. 2506 - 2518
Publisher
MASSACHUSETTS MEDICAL SOC