阿帕鲁胺治疗与前列腺癌无转移生存。
Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.
机构信息
From the Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (M.R.S.); Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal (F.S.); Guy's, King's and St. Thomas' Hospitals, Great Maze Pond, London (S.C.); Georges Pompidou Hospital, Paris (S.O.); University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany (B.A.H.); Veterans Affairs Portland Health Care System, Portland, and Knight Cancer Institute, Oregon Health and Science University, Portland (J.N.G.); Spanish National Cancer Research Center, Madrid, and Hospitales Universitarios Virgen de la Victoria y Regional, Institute of Biomedical Research in Malaga, Malaga - both in Spain (D.O.); Centre for Personalised Nanomedicine, University of Queensland, Brisbane, Australia (P.N.M.); St. Mary's Hospital of Catholic University, Seoul, South Korea (J.Y.L.); Yokohama City University Medical Center, Yokohama, Japan (H.U.); Janssen Research and Development, Los Angeles (A.L.-G., G.C.T., B.M.E., Y.S., Y.C.P., W.R.R., M.K.Y.); and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco (E.J.S.).
出版信息
N Engl J Med. 2018 Apr 12;378(15):1408-1418. doi: 10.1056/NEJMoa1715546. Epub 2018 Feb 8.
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 .).
背景
雄激素受体竞争性抑制剂阿帕鲁胺正在开发用于治疗前列腺癌。我们评估了阿帕鲁胺在有进展为转移高风险的非转移性去势抵抗性前列腺癌（nmCRPC）男性中的疗效。
方法
我们进行了一项双盲、安慰剂对照、3 期临床试验，纳入了前列腺特异性抗原倍增时间为 10 个月或更短的非转移性去势抵抗性前列腺癌男性患者。患者以 2:1 的比例随机分配接受阿帕鲁胺（每天 240mg）或安慰剂治疗。所有患者均继续接受去势治疗。主要终点是无转移生存，定义为从随机分组到影像学上远处转移或死亡的首次检测之间的时间。
结果
共 1207 名男性接受了随机分组（806 名进入阿帕鲁胺组，401 名进入安慰剂组）。在计划的主要分析中，在 378 例事件发生后进行，阿帕鲁胺组的无转移生存中位数为 40.5 个月，安慰剂组为 16.2 个月（转移或死亡的风险比，0.28；95%置信区间[CI]，0.23 至 0.35；P<0.001）。阿帕鲁胺组的症状进展时间明显长于安慰剂组（风险比，0.45；95%CI，0.32 至 0.63；P<0.001）。阿帕鲁胺组因不良事件而停止试验方案的发生率为 10.6%，安慰剂组为 7.0%。阿帕鲁胺组比安慰剂组更常见的不良反应包括皮疹（23.8%比 5.5%）、甲状腺功能减退（8.1%比 2.0%）和骨折（11.7%比 6.5%）。
结论
在非转移性去势抵抗性前列腺癌男性中，与安慰剂相比，阿帕鲁胺可显著延长无转移生存和症状进展时间。（由 Janssen Research and Development 资助；SPARTAN 临床试验.gov 编号，NCT01946204）。
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