局限期小细胞肺癌放化疗后应用度伐利尤单抗。
Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer.
机构信息
From Jilin Cancer Hospital, Changchun (Y. Cheng), Department II of Thoracic Oncology (J.F.) and the Department of Radiation Oncology (A.S.), Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, and the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou (Q.W.) - all in China; Sarah Cannon Research Institute (D.R.S.) and Tennessee Oncology (D.B.D.) - both in Nashville; Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and Chungbuk National University Hospital, Cheongju (K.H.L.) - both in South Korea; Federal State Budgetary Institution "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation, Moscow (K.K.L.); Cancer and Hematology Centers of Western Michigan, Grand Rapids (Y. Chen); National Cancer Center Hospital East, Kashiwa (Y.Z.), and Kyushu University Hospital, Fukuoka (Y.S.) - both in Japan; Hospital Vall d'Hebron and Vall d'Hebron Institute of Oncology, Barcelona (A.N.), and Hospital Universitario Virgen del Rocio, Seville (R.B.) - both in Spain; Hospitals of the City of Cologne, Cologne, Germany (E.L.B.); Chang Gung Medical Foundation-Linkou Branch, Taoyuan, Taiwan (J.W.-C.C.); Akdeniz University Medical Faculty, Antalya, Turkey (S.S.G.); Medical University of Gdansk, Gdansk, Poland (A.B.); National Cancer Hospital, Hanoi, Vietnam (N.T.T.H.); First Faculty of Medicine, Charles University, and General University Hospital, Prague, Czech Republic (M.Z.); AstraZeneca, Cambridge, United Kingdom (H.M.); AstraZeneca, Gaithersburg, MD (H.G., H.J.); and the Department of Radiation Oncology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam (S.S.).
出版信息
N Engl J Med. 2024 Oct 10;391(14):1313-1327. doi: 10.1056/NEJMoa2404873. Epub 2024 Sep 13.
BACKGROUND
Adjuvant therapy with durvalumab, with or without tremelimumab, may have efficacy in patients with limited-stage small-cell lung cancer who do not have disease progression after standard concurrent platinum-based chemoradiotherapy.
METHODS
In a phase 3, double-blind, randomized, placebo-controlled trial, we assigned patients to receive durvalumab at a dose of 1500 mg, durvalumab (1500 mg) plus tremelimumab at a dose of 75 mg (four doses only), or placebo every 4 weeks for up to 24 months. Randomization was stratified according to disease stage (I or II vs. III) and receipt of prophylactic cranial irradiation (yes vs. no). Results of the first planned interim analysis of the two primary end points of overall survival and progression-free survival (assessed on the basis of blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1) with durvalumab as compared with placebo (data cutoff date, January 15, 2024) are reported; results in the durvalumab-tremelimumab group remain blinded.
RESULTS
A total of 264 patients were assigned to the durvalumab group, 200 to the durvalumab-tremelimumab group, and 266 to the placebo group. Durvalumab therapy led to significantly longer overall survival than placebo (median, 55.9 months [95% confidence interval {CI}, 37.3 to not reached] vs. 33.4 months [95% CI, 25.5 to 39.9]; hazard ratio for death, 0.73; 98.321% CI, 0.54 to 0.98; P = 0.01), as well as to significantly longer progression-free survival (median 16.6 months [95% CI, 10.2 to 28.2] vs. 9.2 months [95% CI, 7.4 to 12.9]; hazard ratio for progression or death, 0.76; 97.195% CI, 0.59 to 0.98; P = 0.02). The incidence of adverse events with a maximum grade of 3 or 4 was 24.4% among patients receiving durvalumab and 24.2% among patients receiving placebo; adverse events led to discontinuation in 16.4% and 10.6% of the patients, respectively, and led to death in 2.7% and 1.9%. Pneumonitis or radiation pneumonitis with a maximum grade of 3 or 4 occurred in 3.1% of the patients in the durvalumab group and in 2.6% of those in the placebo group.
CONCLUSIONS
Adjuvant therapy with durvalumab led to significantly longer overall survival and progression-free survival than placebo among patients with limited-stage small-cell lung cancer. (Funded by AstraZeneca; ADRIATIC ClinicalTrials.gov number, NCT03703297.).
背景
在未接受标准同步放化疗后出现疾病进展的局限期小细胞肺癌患者中，与安慰剂相比，度伐利尤单抗联合或不联合替西木单抗辅助治疗可能具有疗效。
方法
在一项 3 期、双盲、随机、安慰剂对照试验中，我们按照疾病分期（Ⅰ或Ⅱ期与Ⅲ期）和是否预防性颅脑照射（是与否）将患者分层，接受 1500mg 剂量的度伐利尤单抗、1500mg 度伐利尤单抗加 75mg 替西木单抗（仅 4 剂）或安慰剂，每 4 周一次，最长 24 个月。根据实体瘤反应评价标准 1.1 版（Response Evaluation Criteria in Solid Tumors， version 1.1），对首次计划进行的两个主要终点（总生存期和无进展生存期）的初步期中分析（数据截止日期为 2024 年 1 月 15 日）进行了报告；度伐利尤单抗-替西木单抗组的结果仍处于盲态。
结果
共 264 例患者被分配至度伐利尤单抗组，200 例患者被分配至度伐利尤单抗-替西木单抗组，266 例患者被分配至安慰剂组。与安慰剂相比，度伐利尤单抗治疗显著延长了总生存期（中位，55.9 个月[95%置信区间（Confidence Interval，CI），37.3 至未达到]与 33.4 个月[95%CI，25.5 至 39.9]；死亡风险比，0.73；98.321%CI，0.54 至 0.98；P=0.01），并显著延长了无进展生存期（中位，16.6 个月[95%CI，10.2 至 28.2]与 9.2 个月[95%CI，7.4 至 12.9]；疾病进展或死亡风险比，0.76；97.195%CI，0.59 至 0.98；P=0.02）。接受度伐利尤单抗治疗的患者中，最严重程度为 3 级或 4 级的不良事件发生率为 24.4%，接受安慰剂治疗的患者中为 24.2%；不良事件分别导致 16.4%和 10.6%的患者停药，分别导致 2.7%和 1.9%的患者死亡。最严重程度为 3 级或 4 级的肺炎或放射性肺炎在度伐利尤单抗组和安慰剂组中分别发生在 3.1%和 2.6%的患者中。
结论
与安慰剂相比，在局限期小细胞肺癌患者中，度伐利尤单抗辅助治疗可显著延长总生存期和无进展生存期。（由阿斯利康公司资助；ADRIATIC 临床试验.gov 编号，NCT03703297。）
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