Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer
- PMID: 29420164
- DOI: 10.1056/NEJMoa1715546
Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer
Abstract
Background: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis.
Methods: We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death.
Results: A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%).
Conclusions: Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo. (Funded by Janssen Research and Development; SPARTAN ClinicalTrials.gov number, NCT01946204 .).
Comment in
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Filling a True Unmet Need: A New Therapy for Nonmetastatic Castrate-resistant Prostate Cancer Commentary on: Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.Urology. 2018 Jun;116:1-2. doi: 10.1016/j.urology.2018.03.007. Epub 2018 Mar 27. Urology. 2018. PMID: 29596865 No abstract available.
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Re: Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.Eur Urol. 2018 Aug;74(2):237-238. doi: 10.1016/j.eururo.2018.03.029. Epub 2018 Apr 10. Eur Urol. 2018. PMID: 29653884 No abstract available.
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Re: Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.Eur Urol. 2018 Aug;74(2):236-237. doi: 10.1016/j.eururo.2018.04.010. Epub 2018 Apr 22. Eur Urol. 2018. PMID: 29691083 No abstract available.
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Apalutamide and Metastasis-free Survival in Prostate Cancer.N Engl J Med. 2018 Jun 28;378(26):2541-2. doi: 10.1056/NEJMc1806189. N Engl J Med. 2018. PMID: 29952180 No abstract available.
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Prostatakarzinom: Apalutamid verlängert metastasenfreies Überleben.Aktuelle Urol. 2019 Feb;50(1):12. doi: 10.1055/a-0770-2761. Epub 2019 Feb 7. Aktuelle Urol. 2019. PMID: 30731495 German. No abstract available.
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Metastases-free survival rate in non-metastatic castration-resistant prostate cancer: Now living on its own!Actas Urol Esp (Engl Ed). 2019 May;43(4):167-168. doi: 10.1016/j.acuro.2019.01.002. Epub 2019 Mar 4. Actas Urol Esp (Engl Ed). 2019. PMID: 30846288 English, Spanish. No abstract available.
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