纳武利尤单抗联合吉西他滨-顺铂治疗晚期尿路上皮癌。
Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma.
机构信息
From the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (M.S.H.); Medical Oncology, Genitourinary Section, Dana-Farber Cancer Institute, Harvard Medical School, Boston (G.S.); the Department of Genitourinary Oncology, Barts Cancer Institute, Queen Mary University of London, London (T.P.); the Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (A.N.); the Department of Oncology, Bradford Hill Clinical Research Center, Santiago, Chile (M.B.); the Department of Medical Oncology, Sf. Nectarie Oncology Center, Department of Oncology, University of Medicine and Pharmacy, Craiova, Romania (M.S.); the Department of Clinical Oncology, Alexander Fleming Institute, Buenos Aires (J.P.S.); the Second Propedeutic Department of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens (A.B.); the Department of Urologic Oncology, Hopital Foch, Suresnes, France (P.B.); the Department of Urology, Eberhard Karls University Tübingen, Tübingen, Germany (J.B.); the Department of Oncology, Akershus University Hospital, Lørenskog, Norway (J.O.); Roswell Park Comprehensive Cancer Center, Buffalo (G.C.), and the Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York (M.D.G.) - both in New York; the Department of Medical Oncology, Ankara University, Ankara, Turkey (Y.Ü.); the Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai (D.Y.), and the Department of Urology, Peking University First Hospital, Beijing (Z.H.) - both in China; the Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Sevilla, Spain (B.P.V.); Seoul National University Hospital, Seoul, South Korea (J.H.K.); the Department of Urology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (Y.T.); Bristol Myers Squibb, Princeton, NJ (J.F., L.W., M.Y.P., F.N.); and Bristol Myers Squibb, Boudry, Switzerland (D.P.).
出版信息
N Engl J Med. 2023 Nov 9;389(19):1778-1789. doi: 10.1056/NEJMoa2309863. Epub 2023 Oct 22.
BACKGROUND
No new agent has improved overall survival in patients with unresectable or metastatic urothelial carcinoma when added to first-line cisplatin-based chemotherapy.
METHODS
In this phase 3, multinational, open-label trial, we randomly assigned patients with previously untreated unresectable or metastatic urothelial carcinoma either to receive intravenous nivolumab (at a dose of 360 mg) plus gemcitabine-cisplatin (nivolumab combination) every 3 weeks for up to six cycles, followed by nivolumab (at a dose of 480 mg) every 4 weeks for a maximum of 2 years, or to receive gemcitabine-cisplatin alone every 3 weeks for up to six cycles. The primary outcomes were overall and progression-free survival. The objective response and safety were exploratory outcomes.
RESULTS
A total of 608 patients underwent randomization (304 to each group). At a median follow-up of 33.6 months, overall survival was longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for death, 0.78; 95% confidence interval [CI], 0.63 to 0.96; P = 0.02); the median survival was 21.7 months (95% CI, 18.6 to 26.4) as compared with 18.9 months (95% CI, 14.7 to 22.4), respectively. Progression-free survival was also longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for progression or death, 0.72; 95% CI, 0.59 to 0.88; P = 0.001). The median progression-free survival was 7.9 months and 7.6 months, respectively. At 12 months, progression-free survival was 34.2% and 21.8%, respectively. The overall objective response was 57.6% (complete response, 21.7%) with nivolumab-combination therapy and 43.1% (complete response, 11.8%) with gemcitabine-cisplatin alone. The median duration of complete response was 37.1 months with nivolumab-combination therapy and 13.2 months with gemcitabine-cisplatin alone. Grade 3 or higher adverse events occurred in 61.8% and 51.7% of the patients, respectively.
CONCLUSIONS
Combination therapy with nivolumab plus gemcitabine-cisplatin resulted in significantly better outcomes in patients with previously untreated advanced urothelial carcinoma than gemcitabine-cisplatin alone. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 901 ClinicalTrials.gov number, NCT03036098.).
背景
在转移性或不可切除的尿路上皮癌患者中，添加新的药物不能改善其总生存期。
方法
在这项 3 期、多国、开放性试验中，我们将未经治疗的转移性或不可切除的尿路上皮癌患者随机分配至纳武利尤单抗（360mg 静脉注射）+吉西他滨-顺铂（纳武利尤单抗联合治疗）组，每 3 周治疗 6 个周期，随后每 4 周治疗 2 年（纳武利尤单抗剂量为 480mg）；或吉西他滨-顺铂组，每 3 周治疗 6 个周期。主要终点是总生存期和无进展生存期。客观缓解和安全性是探索性终点。
结果
共有 608 名患者接受了随机分组（每组 304 名）。中位随访 33.6 个月时，纳武利尤单抗联合治疗组的总生存期长于吉西他滨-顺铂组（死亡风险比，0.78；95%置信区间[CI]，0.63 至 0.96；P=0.02）；中位生存期分别为 21.7 个月（95%CI，18.6 至 26.4）和 18.9 个月（95%CI，14.7 至 22.4）。纳武利尤单抗联合治疗组的无进展生存期也长于吉西他滨-顺铂组（进展或死亡风险比，0.72；95%CI，0.59 至 0.88；P=0.001）。中位无进展生存期分别为 7.9 个月和 7.6 个月。12 个月时，无进展生存率分别为 34.2%和 21.8%。纳武利尤单抗联合治疗组的总客观缓解率为 57.6%（完全缓解率，21.7%），吉西他滨-顺铂组为 43.1%（完全缓解率，11.8%）。纳武利尤单抗联合治疗组完全缓解的中位持续时间为 37.1 个月，吉西他滨-顺铂组为 13.2 个月。61.8%和 51.7%的患者分别发生了 3 级或更高级别的不良事件。
结论
与吉西他滨-顺铂相比，纳武利尤单抗联合吉西他滨-顺铂治疗未经治疗的晚期尿路上皮癌患者的结局显著改善。（由 Bristol Myers Squibb 和小野制药公司资助；CheckMate 901 临床试验.gov 编号，NCT03036098）。
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