可手术膀胱癌新辅助化疗联合围手术期 durvalumab 治疗。
Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer.
机构信息
From Barts Cancer Institute, Queen Mary University of London, Barts Health NHS Trust Biomedical Research Centre, London (T.P.), the Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (J.W.F.C.), and AstraZeneca, Cambridge (J.A.) - all in the United Kingdom; the Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (M.D.G.), the Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center (H.A.-A.), and AstraZeneca (A.G.) - all in New York; the Departments of Urology and Biochemistry, Northwestern University Feinberg School of Medicine, Chicago (J.J.M.); the University of Tsukuba, Tsukuba, Japan (H.N.); Internal Medical 3, Vietnam National Cancer Hospital, Hanoi (T.Q.V.); the Department of Experimental and Clinical Medicine, University of Florence, and the Medical Oncology Unit, Careggi University Hospital - both in Florence, Italy (L.A.); Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland (P.W.); the Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia (V.A.); Hospital Alemão Oswaldo Cruz, Sao Paulo (A.G.K.); the Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, South Korea (T-H.K.); Medical Oncology, Vall d´Hebron Institute of Oncology, Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona (C.S.); the Department of Urology, China Medical University Hospital and School of Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan (C-H.C.); the Department of Urology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany (F.R.); Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey (M.Ö.); BC Cancer-Vancouver, Vancouver, BC, Canada (B.J.E.); Mater Hospital Brisbane, Mater Misericordiae, and the School of Clinical Medicine, Mater Clinical Unit, University of Queensland - both in Brisbane, Australia (N.O.); the Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic (T.B.); the Institute of Oncology, Sheba Medical Center, Ramat Gan, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv - both in Israel (M.G.); the University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City (Y.Z.); AstraZeneca, Gaithersburg, MD (S.H.); and the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (M.S.H.).
出版信息
N Engl J Med. 2024 Nov 14;391(19):1773-1786. doi: 10.1056/NEJMoa2408154. Epub 2024 Sep 15.
BACKGROUND
Neoadjuvant chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer. Adding perioperative immunotherapy may improve outcomes.
METHODS
In this phase 3, open-label, randomized trial, we assigned, in a 1:1 ratio, cisplatin-eligible patients with muscle-invasive bladder cancer to receive neoadjuvant durvalumab plus gemcitabine-cisplatin every 3 weeks for four cycles, followed by radical cystectomy and adjuvant durvalumab every 4 weeks for eight cycles (durvalumab group), or to receive neoadjuvant gemcitabine-cisplatin followed by radical cystectomy alone (comparison group). Event-free survival was one of two primary end points. Overall survival was the key secondary end point.
RESULTS
In total, 533 patients were assigned to the durvalumab group and 530 to the comparison group. The estimated event-free survival at 24 months was 67.8% (95% confidence interval [CI], 63.6 to 71.7) in the durvalumab group and 59.8% (95% CI, 55.4 to 64.0) in the comparison group (hazard ratio for progression, recurrence, not undergoing radical cystectomy, or death from any cause, 0.68; 95% CI, 0.56 to 0.82; P<0.001 by stratified log-rank test). The estimated overall survival at 24 months was 82.2% (95% CI, 78.7 to 85.2) in the durvalumab group and 75.2% (95% CI, 71.3 to 78.8) in the comparison group (hazard ratio for death, 0.75; 95% CI, 0.59 to 0.93; P = 0.01 by stratified log-rank test). Treatment-related adverse events of grade 3 or 4 in severity occurred in 40.6% of the patients in the durvalumab group and in 40.9% of those in the comparison group; treatment-related adverse events leading to death occurred in 0.6% in each group. Radical cystectomy was performed in 88.0% of the patients in the durvalumab group and in 83.2% of those in the comparison group.
CONCLUSIONS
Perioperative durvalumab plus neoadjuvant chemotherapy led to significant improvements in event-free survival and overall survival as compared with neoadjuvant chemotherapy alone. (Funded by AstraZeneca; NIAGARA ClinicalTrials.gov number, NCT03732677; EudraCT number, 2018-001811-59.).
背景
新辅助化疗后行根治性膀胱切除术是顺铂治疗有效的肌层浸润性膀胱癌患者的标准治疗方法。添加围手术期免疫治疗可能会改善结果。
方法
在这项 3 期、开放标签、随机试验中，我们按照 1:1 的比例将顺铂治疗有效的肌层浸润性膀胱癌患者分配至接受新辅助度伐利尤单抗联合吉西他滨-顺铂每 3 周治疗 4 个周期，随后行根治性膀胱切除术和辅助度伐利尤单抗每 4 周治疗 8 个周期（度伐利尤单抗组），或接受新辅助吉西他滨-顺铂治疗后单独行根治性膀胱切除术（对照组）。无事件生存是两个主要终点之一。总生存是关键次要终点。
结果
共有 533 例患者被分配至度伐利尤单抗组，530 例患者被分配至对照组。24 个月时的估计无事件生存率为度伐利尤单抗组 67.8%（95%置信区间 [CI]，63.6 至 71.7），对照组 59.8%（95% CI，55.4 至 64.0）（进展、复发、未行根治性膀胱切除术或任何原因导致的死亡的风险比，0.68；95%CI，0.56 至 0.82；分层对数秩检验 P<0.001）。24 个月时的估计总生存率为度伐利尤单抗组 82.2%（95% CI，78.7 至 85.2），对照组 75.2%（95% CI，71.3 至 78.8）（死亡风险比，0.75；95%CI，0.59 至 0.93；分层对数秩检验 P=0.01）。度伐利尤单抗组中 40.6%的患者和对照组中 40.9%的患者发生了 3 级或 4 级严重程度的治疗相关不良事件；两组各有 0.6%的患者因治疗相关不良事件导致死亡。度伐利尤单抗组中 88.0%的患者和对照组中 83.2%的患者行根治性膀胱切除术。
结论
与新辅助化疗相比，围手术期度伐利尤单抗联合新辅助化疗可显著改善无事件生存率和总生存率。（由阿斯利康公司资助；NIAGARA 临床试验.gov 编号，NCT03732677；EudraCT 编号，2018-001811-59。）
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