Ramaswamy Govindan, Washington University School of Medicine, St Louis, MO; Aleksandra Szczesna, Mazowieckie Centrum Leczenia Chorób Płuc i Gruźlicy, Otwock; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; Myung-Ju Ahn, Samsung Medical Center, Sungkyunkwan University, Seoul; Ki Hyeong Lee, Chungbuk National University Hospital, Cheongju-si, Republic of Korea; Claus-Peter Schneider, Zentralklinik Bad Berka, Bad Berka; Joachim Von Pawel, Asklepius Fachkliniken, Gauting; Martin Reck, LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany; Pablo Fernando Gonzalez Mella, Centro de Investigaciones Clinicas, Universidad de Valparaíso and Fundación Arturo López Pérez, Santiago, Chile; Fabrice Barlesi, Aix Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille, France; Baohui Han, Shanghai Chest Hospital Affiliated to Shanghai JiaoTong University, Shanghai; Li Zhang, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China; Doina Elena Ganea, Spitalul Judetean De Urgenta Suceava, Sfântul loan cel Nou, Suceava, Romania; Vladimir Vladimirov, State Healthcare Institute, Pyatigorsk Oncology Dispensary, Pyatigorsk; Natalia Fadeeva, Chelyabinsk Regional Oncology Dispensary, Chelyabinsk, Russian Federation; Takayasu Kurata, Kansai Medical University Hirakata Hospital, Osaka; Tomohide Tamura, St Luke's International Hospital, Tokyo, Japan; Pieter E. Postmus, University of Liverpool, Liverpool, United Kingdom; Kenneth O'Byrne, Princess Alexandra Hospital and Queensland University of Technology, Brisbane, Queensland, Australia; and Justin Kopit, Mingshun Li, and Marina Tschaika, Bristol-Myers Squibb, Princeton, NJ.
J Clin Oncol. 2017 Oct 20;35(30):3449-3457. doi: 10.1200/JCO.2016.71.7629. Epub 2017 Aug 30.
Purpose Patients with squamous non-small-cell lung cancer (NSCLC) have poor prognosis and limited treatment options. This randomized, double-blind, phase III study investigated the efficacy and safety of first-line ipilimumab or placebo plus paclitaxel and carboplatin in advanced squamous NSCLC. Patients and Methods Patients with stage IV or recurrent chemotherapy-naïve squamous NSCLC were randomly assigned (1:1) to receive paclitaxel and carboplatin plus blinded ipilimumab 10 mg/kg or placebo every 3 weeks on a phased induction schedule comprising six chemotherapy cycles, with ipilimumab or placebo from cycles 3 to 6 and then, after induction treatment, ipilimumab or placebo maintenance every 12 weeks for patients with stable disease or better. The primary end point was overall survival (OS) in patients receiving at least one dose of blinded study therapy. Results Of 956 randomly assigned patients, 749 received at least one dose of blinded study therapy (chemotherapy plus ipilimumab, n = 388; chemotherapy plus placebo, n = 361). Median OS was 13.4 months for chemotherapy plus ipilimumab and 12.4 months for chemotherapy plus placebo (hazard ratio, 0.91; 95% CI, 0.77 to 1.07; P = .25). Median progression-free survival was 5.6 months for both groups (hazard ratio, 0.87; 95% CI, 0.75 to 1.01). Rates of grade 3 or 4 treatment-related adverse events (TRAEs), any-grade serious TRAEs, and TRAEs leading to discontinuation were numerically higher with chemotherapy plus ipilimumab (51%, 33%, and 28%, respectively) than with chemotherapy plus placebo (35%, 10%, and 7%, respectively). Seven treatment-related deaths occurred with chemotherapy plus ipilimumab, and one occurred with chemotherapy plus placebo. Conclusion The addition of ipilimumab to first-line chemotherapy did not prolong OS compared with chemotherapy alone in patients with advanced squamous NSCLC. The safety profile of chemotherapy plus ipilimumab was consistent with that observed in previous lung and melanoma studies. Ongoing studies are evaluating ipilimumab in combination with nivolumab in this population.
患有鳞状非小细胞肺癌（NSCLC）的患者预后较差，治疗选择有限。这项随机、双盲、III 期研究调查了一线伊匹单抗或安慰剂联合紫杉醇和卡铂治疗晚期鳞状 NSCLC 的疗效和安全性。
IV 期或复发性化疗初治的鳞状 NSCLC 患者按 1:1 随机分配（分层随机），接受紫杉醇和卡铂联合盲法伊匹单抗 10mg/kg 或安慰剂，每 3 周 1 次，方案包括 6 个化疗周期，伊匹单抗或安慰剂从第 3 周期至第 6 周期，然后对于疾病稳定或更好的患者，在诱导治疗后，每 12 周给予伊匹单抗或安慰剂维持治疗。主要终点是接受至少 1 剂盲法研究治疗的患者的总生存期（OS）。
956 例随机分配的患者中，749 例至少接受了 1 剂盲法研究治疗（化疗加伊匹单抗，n=388；化疗加安慰剂，n=361）。化疗加伊匹单抗组的中位 OS 为 13.4 个月，化疗加安慰剂组为 12.4 个月（风险比，0.91；95%CI，0.77 至 1.07；P=0.25）。两组的中位无进展生存期均为 5.6 个月（风险比，0.87；95%CI，0.75 至 1.01）。化疗加伊匹单抗组的 3 级或 4 级治疗相关不良事件（TRAEs）、任何级别严重 TRAEs 和因 TRAE 而停药的发生率均高于化疗加安慰剂组（分别为 51%、33%和 28%，而化疗加安慰剂组分别为 35%、10%和 7%）。化疗加伊匹单抗组有 7 例治疗相关死亡，化疗加安慰剂组有 1 例。
与单独化疗相比，伊匹单抗联合一线化疗并未延长晚期鳞状 NSCLC 患者的 OS。化疗加伊匹单抗的安全性与先前的肺癌和黑色素瘤研究一致。目前正在研究该人群中伊匹单抗联合纳武单抗的疗效。
