From the H. Lee Moffitt Cancer Center and Research Institute, Tampa (S.J.A., A.C., J.E.G.), Cancer Specialists of North Florida, Jacksonville (A.V.), Florida Cancer Specialists, Fleming Island (A.V.), and Florida Hospital Cancer Institute, Orlando (T.M.) - all in Florida; Tennessee Oncology, Chattanooga (D.D.), and Sarah Cannon Research Institute, Nashville (D.D., D.R.S.) - both in Tennessee; Hospital Universitario Virgen Macarena, Seville (D.V.), and Hospital Universitario 12 de Octubre, CiberOnc, Universidad Complutense and Spanish National Cancer Research Center (L.P.-A.), and Hospital Universitario La Paz (J.C.C.), Madrid - all in Spain; Kanagawa Cancer Center, Yokohama (S.M.), Kansai Medical University Hospital, Hirakata (T.K.), Kurume University Hospital, Kurume (T.T.), and Nippon Medical School Hospital, Tokyo (K.K.) - all in Japan; Westmead Hospital and the University of Sydney, Sydney (R.H.), and Flinders University and Flinders Medical Centre, Adelaide, SA (C.S.K.) - all in Australia; Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju (K.H.L.), Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju (Y.-C.K.) - all in South Korea; Vivantes Klinikum Neukoelln, Berlin (M.W.), and the Lung Clinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf (M.R.) - both in Germany; Centre Hospitalier Universitaire de Liège, Liège (M.B.), and University Hospitals KU Leuven, Leuven (J.V.) - both in Belgium; Centre Hospitalier Universitaire de Montpellier and Institut du Cancer de Montpellier Val d'Aurelle, Montpellier (X.Q.), Institut Gustave Roussy, Villejuif (D.P.), and Institut de Cancérologie de l'Ouest-site René Gauducheau, Saint Herblain (S.H.) - all in France; National Koranyi Institute of Pulmonology, Budapest, Hungary (G.O.); the University of Manchester and the Christie NHS Foundation Trust, Manchester (C.F.-F.), AstraZeneca, Alderley Park (C.W.), and AstraZeneca, Cambridge (M.T.) - all in the United Kingdom; AstraZeneca, Gaithersburg, MD (G.M., P.A.D.); and Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Istanbul, Turkey (M.Ö.).
N Engl J Med. 2018 Dec 13;379(24):2342-2350. doi: 10.1056/NEJMoa1809697. Epub 2018 Sep 25.
An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression-free survival, as compared with placebo, among patients with stage III, unresectable non-small-cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. Here we report the results for the second primary end point of overall survival.
We randomly assigned patients, in a 2:1 ratio, to receive durvalumab intravenously, at a dose of 10 mg per kilogram of body weight, or matching placebo every 2 weeks for up to 12 months. Randomization occurred 1 to 42 days after the patients had received chemoradiotherapy and was stratified according to age, sex, and smoking history. The primary end points were progression-free survival (as assessed by blinded independent central review) and overall survival. Secondary end points included the time to death or distant metastasis, the time to second progression, and safety.
Of the 713 patients who underwent randomization, 709 received the assigned intervention (473 patients received durvalumab and 236 received placebo). As of March 22, 2018, the median follow-up was 25.2 months. The 24-month overall survival rate was 66.3% (95% confidence interval [CI], 61.7 to 70.4) in the durvalumab group, as compared with 55.6% (95% CI, 48.9 to 61.8) in the placebo group (two-sided P=0.005). Durvalumab significantly prolonged overall survival, as compared with placebo (stratified hazard ratio for death, 0.68; 99.73% CI, 0.47 to 0.997; P=0.0025). Updated analyses regarding progression-free survival were similar to those previously reported, with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group (stratified hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.63). The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group (stratified hazard ratio, 0.53; 95% CI, 0.41 to 0.68). A total of 30.5% of the patients in the durvalumab group and 26.1% of those in the placebo group had grade 3 or 4 adverse events of any cause; 15.4% and 9.8% of the patients, respectively, discontinued the trial regimen because of adverse events.
Durvalumab therapy resulted in significantly longer overall survival than placebo. No new safety signals were identified. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461 .).
在这项 3 期试验的早期分析中，与安慰剂相比，durvalumab 显著延长了未发生疾病进展的同步放化疗后不可切除的 III 期非小细胞肺癌（NSCLC）患者的无进展生存期。在此，我们报告了总体生存的第二个主要终点结果。
我们以 2:1 的比例随机分配患者，接受静脉注射 durvalumab，剂量为每千克体重 10 毫克，或每 2 周匹配安慰剂，最长 12 个月。随机化发生在患者接受放化疗后 1 至 42 天，按年龄、性别和吸烟史分层。主要终点为无进展生存期（由盲法独立中心审查评估）和总生存期。次要终点包括死亡或远处转移时间、第二次进展时间和安全性。
713 名接受随机分组的患者中，709 名接受了指定的干预措施（473 名接受 durvalumab，236 名接受安慰剂）。截至 2018 年 3 月 22 日，中位随访时间为 25.2 个月。durvalumab 组的 24 个月总生存率为 66.3%（95%置信区间[CI]，61.7 至 70.4），安慰剂组为 55.6%（95%CI，48.9 至 61.8）（双侧 P=0.005）。durvalumab 与安慰剂相比，显著延长了总生存期（死亡风险分层 HR，0.68；99.73%CI，0.47 至 0.997；P=0.0025）。关于无进展生存期的更新分析与之前报告的结果相似，durvalumab 组的中位无进展生存期为 17.2 个月，安慰剂组为 5.6 个月（疾病进展或死亡风险分层 HR，0.51；95%CI，0.41 至 0.63）。durvalumab 组死亡或远处转移的中位时间为 28.3 个月，安慰剂组为 16.2 个月（分层 HR，0.53；95%CI，0.41 至 0.68）。durvalumab 组有 30.5%的患者和安慰剂组有 26.1%的患者发生任何原因的 3 级或 4 级不良事件；分别有 15.4%和 9.8%的患者因不良事件停止试验方案。
与安慰剂相比，durvalumab 治疗显著延长了总生存期。未发现新的安全性信号。（由阿斯利康公司资助；PACIFIC 临床试验注册编号，NCT02125461）。
