@article{8963ac4d4d534409be5b114034c4c78d,
title = "Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer",
abstract = "Background: In the SPARTAN study, compared with placebo, apalutamide added to ongoing androgen deprivation therapy significantly prolonged metastasis-free survival (MFS) and time to symptomatic progression in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC). Overall survival (OS) results at the first interim analysis (IA1) were immature, with 104 of 427 (24%) events required for planned final OS analysis. Here, we report the results of a second pre-specified interim analysis (IA2). Methods: One thousand two hundred and seven patients with nmCRPC were randomized 2-:-1 to apalutamide (240-mg daily) or placebo. The primary end point of the study was MFS. Subsequent therapy for metastatic CRPC was permitted. When the primary end point was met, the study was unblinded. Patients receiving placebo who had not yet developed metastases were offered open-label apalutamide. At IA2, pre-specified analysis of OS was undertaken, using a group-sequential testing procedure with O'Brien–Fleming-type alpha spending function. Safety and second progression-free survival (PFS2) were assessed. Results: Median follow-up was 41-months. With 285 (67% of required) OS events, apalutamide was associated with an improved OS compared with placebo (HR 0.75; 95% CI 0.59–0.96; P-=-0.0197), although the P-value did not cross the pre-specified O'Brien–Fleming boundary of 0.0121. Apalutamide improved PFS2 (HR 0.55; 95% CI 0.45–0.68). At IA2, 69% of placebo-treated and 40% of apalutamide-treated patients had received subsequent life-prolonging therapy for metastatic CRPC. No new safety signals were observed. Conclusion: In patients with nmCRPC, apalutamide was associated with a 25% reduction in risk of death compared with placebo. This OS benefit was observed despite crossover of placebo-treated patients and higher rates of subsequent life-prolonging therapy for the placebo group.",
keywords = "apalutamide, non-metastatic castration-resistant prostate cancer, overall survival, subsequent therapy",
author = "Small, {E. J.} and F. Saad and S. Chowdhury and S. Oudard and Hadaschik, {B. A.} and Graff, {J. N.} and D. Olmos and Mainwaring, {P. N.} and Lee, {J. Y.} and H. Uemura and {De Porre}, P. and Smith, {A. A.} and K. Zhang and A. Lopez-Gitlitz and Smith, {M. R.}",
note = "Funding Information: The SPARTAN study was funded by Janssen Research & Development. Editorial assistance was provided by William Turner, PhD, of Parexel, with funding from Janssen Global Services, LLC (no grant numbers apply). Funding Information: The authors would like to thank the patients who participated in this trial, and their families, as well as the investigators, study coordinators, study teams and nurses. Statistical input was provided by Youyi Shu, PhD, of Janssen Research & Development. The SPARTAN study was funded by Janssen Research & Development. Editorial assistance was provided by William Turner, PhD, of Parexel, with funding from Janssen Global Services, LLC (no grant numbers apply). Janssen Research & Development10.13039/100005205, Janssen Global Services, LLC, EJS reports advisory roles for Fortis and Janssen Oncology; travel from Janssen; stock and interest in Fortis and Harpoon Therapeutics; honoraria from Janssen; and research funding from Janssen. FS reports advisory roles for Astellas Pharma, Janssen Oncology, Sanofi, AstraZeneca/MedImmune and Bayer; honoraria from Astellas Pharma, Janssen Oncology, Sanofi, Bayer, AstraZeneca, Amgen and AbbVie; and research funding from Astellas Pharma, Bayer, Janssen Oncology, Sanofi, AstraZeneca, Pfizer and Bristol-Myers Squibb. SC reports advisory roles for Clovis Oncology, Astellas Pharma, Bayer, Pfizer and Janssen-Cilag; stock in Curve Life; speakers' bureau for Pfizer; honoraria from Clovis Oncology and Novartis; and research funding from Sanofi/Aventis and Clovis Oncology. SO reports advisory roles for Pfizer, Bayer, Merck, Bristol-Myers Squibb, Novartis, Eisai, Sanofi, Janssen and Astellas Pharma; travel from Pfizer, Bayer, Merck, Bristol-Myers Squibb, Novartis and Eisai; honoraria from Pfizer, Bayer, Merck, Bristol-Myers Squibb, Novartis, Eisai, Sanofi, Astellas Pharma and Janssen; and research funding from Ipsen and Sanofi. BAH reports advisory roles for Bayer, Lightpoint Medical, Inc. Janssen R&D, Bristol-Myers-Squibb and Astellas; research funding from Profound Medical, German Cancer Aid, German Research Foundation, Janssen R&D, Bristol-Myers-Squibb and Astellas; and travel from AstraZeneca, Janssen R&D and Astellas. JNG reports an advisory role for Exelixis; travel from Bayer, Merck Sharp & Dohme and Clovis Oncology; patents, royalties and intellectual property with Oncoresponse: Exceptional Responders; honoraria from Bayer, Astellas Medivation and Janssen Oncology; and research funding from Sanofi, Medivation, Bristol-Myers Squibb, Merck Sharp & Dohme and Janssen Oncology. DO reports advisory roles for Janssen, Bayer, AstraZeneca and Clovis Oncology; travel from Bayer, Janssen and Ipsen; honoraria from Bayer, Janssen and Sanofi; and research funding from AstraZeneca, Bayer, Janssen, Genentech/Roche, Pfizer, Astellas Medivation and Tokai Pharmaceuticals. PNM reports an advisory role with Pfizer; speakers' bureau with Ipsen, Roche/Genentech, Pfizer, Janssen Oncology, Medivation/Astellas, Merck and Novartis; travel for Ipsen, Roche/Genentech, Pfizer, Janssen Oncology, Medivation/Astellas, Merck and Novartis; stock and interests with Xing Technologies; honoraria from Ipsen, Roche/Genentech, Pfizer, Janssen Oncology, Medivation/Astellas, Merck and Novartis; and research funding from Merck KGaA. JYL declares no conflicts of interest. HU reports advisory roles for Janssen Oncology, Bayer, Astellas, Sanofi, Takeda and AstraZeneca, and honoraria from Dai-ichi Sankyo, Kirin Kyowa-hakkou and Fujifilm-Toyama Chemistry. PDP, AAS, KZ, and AL-G are current or former employees of Janssen Research & Development and hold/held stock in Johnson & Johnson. MRS reports advisory roles for Bayer, Janssen Oncology, Amgen, Pfizer, Lilly and Novartis; travel for Amgen, Bayer, Janssen and Lilly; and research funding from Janssen Oncology, Gilead Sciences and Bayer. Note: This study was published in tandem with presentation at the 2019 European Society for Medical Oncology (ESMO) Annual Congress, September 27?October 1, Barcelona, Spain. Publisher Copyright: {\textcopyright} 2019 THE AUTHORS",
year = "2019",
month = nov,
doi = "10.1093/annonc/mdz397",
language = "English (US)",
volume = "30",
pages = "1813--1820",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "11",
}