Increased survival with enzalutamide in prostate cancer after chemotherapy - PubMed (original) (raw)
Clinical Trial
. 2012 Sep 27;367(13):1187-97.
doi: 10.1056/NEJMoa1207506. Epub 2012 Aug 15.
Karim Fizazi, Fred Saad, Mary-Ellen Taplin, Cora N Sternberg, Kurt Miller, Ronald de Wit, Peter Mulders, Kim N Chi, Neal D Shore, Andrew J Armstrong, Thomas W Flaig, Aude Fléchon, Paul Mainwaring, Mark Fleming, John D Hainsworth, Mohammad Hirmand, Bryan Selby, Lynn Seely, Johann S de Bono; AFFIRM Investigators
Collaborators, Affiliations
- PMID: 22894553
- DOI: 10.1056/NEJMoa1207506
Free article
Clinical Trial
Increased survival with enzalutamide in prostate cancer after chemotherapy
Howard I Scher et al. N Engl J Med. 2012.
Free article
Abstract
Background: Enzalutamide (formerly called MDV3100) targets multiple steps in the androgen-receptor-signaling pathway, the major driver of prostate-cancer growth. We aimed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy.
Methods: In our phase 3, double-blind, placebo-controlled trial, we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity. We randomly assigned them, in a 2:1 ratio, to receive oral enzalutamide at a dose of 160 mg per day (800 patients) or placebo (399 patients). The primary end point was overall survival.
Results: The study was stopped after a planned interim analysis at the time of 520 deaths. The median overall survival was 18.4 months (95% confidence interval [CI], 17.3 to not yet reached) in the enzalutamide group versus 13.6 months (95% CI, 11.3 to 15.8) in the placebo group (hazard ratio for death in the enzalutamide group, 0.63; 95% CI, 0.53 to 0.75; P<0.001). The superiority of enzalutamide over placebo was shown with respect to all secondary end points: the proportion of patients with a reduction in the prostate-specific antigen (PSA) level by 50% or more (54% vs. 2%, P<0.001), the soft-tissue response rate (29% vs. 4%, P<0.001), the quality-of-life response rate (43% vs. 18%, P<0.001), the time to PSA progression (8.3 vs. 3.0 months; hazard ratio, 0.25; P<0.001), radiographic progression-free survival (8.3 vs. 2.9 months; hazard ratio, 0.40; P<0.001), and the time to the first skeletal-related event (16.7 vs. 13.3 months; hazard ratio, 0.69; P<0.001). Rates of fatigue, diarrhea, and hot flashes were higher in the enzalutamide group. Seizures were reported in five patients (0.6%) receiving enzalutamide.
Conclusions: Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy. (Funded by Medivation and Astellas Pharma Global Development; AFFIRM ClinicalTrials.gov number, NCT00974311.).
Comment in
- Enzalutamide--a major advance in the treatment of metastatic prostate cancer.
Vogelzang NJ. Vogelzang NJ. N Engl J Med. 2012 Sep 27;367(13):1256-7. doi: 10.1056/NEJMe1209041. N Engl J Med. 2012. PMID: 23013078 No abstract available. - Enzalutamide (formerly MDV3100) as a new therapeutic option for men with metastatic castration-resistant prostate cancer.
Aragon-Ching JB. Aragon-Ching JB. Asian J Androl. 2012 Nov;14(6):805-6. doi: 10.1038/aja.2012.113. Epub 2012 Oct 8. Asian J Androl. 2012. PMID: 23042445 Free PMC article. - Re: Increased survival with enzalutamide in prostate cancer after chemotherapy.
Taneja SS. Taneja SS. J Urol. 2013 Jan;189(1):123-4. doi: 10.1016/j.juro.2012.10.050. Epub 2012 Nov 16. J Urol. 2013. PMID: 23235213 No abstract available. - Enzalutamide in prostate cancer after chemotherapy.
Berruti A, Generali D, Tampellini M. Berruti A, et al. N Engl J Med. 2012 Dec 20;367(25):2448; author reply 2448-9. doi: 10.1056/NEJMc1212940. N Engl J Med. 2012. PMID: 23252532 No abstract available.
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