TY - JOUR
T1 - Apalutamide treatment and metastasis-free survival in prostate cancer
AU - Smith, Matthew R.
AU - Saad, Fred
AU - Chowdhury, Simon
AU - Oudard, Stéphane
AU - Hadaschik, Boris A.
AU - Graff, Julie N.
AU - Olmos, David
AU - Mainwaring, Paul N.
AU - Lee, Ji Youl
AU - Uemura, Hiroji
AU - Lopez-Gitlitz, Angela
AU - Trudel, Géralyn C.
AU - Espina, Byron M.
AU - Shu, Youyi
AU - Park, Youn C.
AU - Rackoff, Wayne R.
AU - Yu, Margaret K.
AU - Small, Eric J.
N1 - Funding Information:
Supported by Janssen Research and Development. (Aragon Pharmaceuticals is a wholly owned subsidiary of Johnson & Johnson. Janssen Research and Development is part of the Jans-sen Pharmaceutical Companies of Johnson & Johnson and provides various services to its affiliated company, Aragon Pharmaceuticals.) Dr. Smith reports consulting fees from Astellas and Bayer; Dr. Saad, receiving grant support, honoraria, consulting fees, lecture fees, and writing assistance from Janssen, Astellas, Sanofi, and Bayer; Dr. Chowdhury, receiving honoraria, consulting fees, fees for serving on a speakers’ bureau, and travel support from Johnson & Johnson and Astellas, honoraria, consulting fees, and fees for serving on a speakers’ bureau from Sanofi, and grant support, honoraria, consulting fees, and fees for serving on a speakers’ bureau from Clovis Oncology; Dr. Oudard, receiving honoraria and lecture fees from Sanofi, Astellas, and Bayer; Dr. Hadaschik, receiving grant support, consulting fees, and travel support from Janssen and Astellas, grant support and consulting fees from Bristol-Myers Squibb, consulting fees and travel support from Bayer, and grant support from Profound Medical; Dr. Graff, receiving grant support and consulting fees from Janssen and Astellas, consulting fees and lecture fees from Bayer, grant support and consulting fees from Sanofi, grant support from Merck and Bristol-Myers Squibb, and consulting fees from Dendreon; Dr. Olmos, receiving grant support and consulting fees from Janssen, Astellas, Bayer, Sanofi, and Genentech and grant support from AstraZeneca; Dr. Mainwaring, receiving honoraria, consulting fees, fees for serving on a speakers’ bureau, and travel support from Ipsen, Janssen, Novartis, Pfizer, and Roche, grant support, honoraria, consulting fees, fees for serving on a speakers’ bureau, and travel support from Merck, and fees for leadership and travel support from Xing Technologies, owning stock in Xing Technologies, and holding a pending patent (WO2014093357) on cell-free biofragment compositions and related systems, devices, and methods, a pending patent (WO2014127409) on a device and method for the detection of target entities, and a pending patent (WO2015095929) on a nucleic-acid detection method and kit; Dr. Uemura, receiving honoraria and travel support from Janssen, Sanofi, and Bayer, honoraria from Astellas, honoraria, consulting fees, and travel support from Takeda, and consulting fees from AstraZeneca; Dr. Lopez-Gitlitz, Dr. Trudel, Mr. Espina, Mr. Shu, Dr. Park, and Dr. Yu, being employed by Janssen Research and Development and owning stock in Johnson & Johnson; and Dr. Rackoff, being employed by and owning stock in Johnson & Johnson. No other potential conflict of interest relevant to this article was reported.
Publisher Copyright:
Copyright © 2018 Massachusetts Medical Society.
PY - 2018/4/12
Y1 - 2018/4/12
N2 - 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.)
AB - 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.)
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U2 - 10.1056/NEJMoa1715546
DO - 10.1056/NEJMoa1715546
M3 - Article
C2 - 29420164
AN - SCOPUS:85045420475
SN - 0028-4793
VL - 378
SP - 1408
EP - 1418
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 15
ER -