Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer
Authors: Cheng Ying , Han Liang , Wu Lin , Chen Jun , Sun Hongmei , Wen Guilan , Ji Yinghua , Dvorkin Mikhail , Shi Jianhua , Pan Zhijie , Shi Jinsheng , Wang Xicheng , Bai Yuansong , Melkadze Tamar , Pan Yueyin , Min Xuhong , Viguro Maksym , Li Xingya , Zhao Yanqiu , Yang Junquan , Makharadze Tamta , Arkania Ekaterine , Kang Wenying , Wang Qingyu , Zhu Jun ,   ASTRUM-005 Study Group, Ren Xiubao , Kuchava Vladimer , Sun Guoping , Li Gaofeng , Lin Wen , Zhang Tao , Harputluoglu Hakan , Cicin Irfan , Feng Guosheng , Hao Yanrong , Ying Kejing , Sun Ping , Zhong Aihong , An Guangyu , Wang Yan , Chen Chun , Yang Sheng , Chen Zhendong , Penkov Konstantin , Semegen Yuriy , Kobziev Oleg , Luo Feng , Cao Peiguo , Yang Zhixiong , Fan Min , Li Wen , Mroz Robert , Akopov Andrey , Goksel Tuncay , Gumus Mahmut , Zhuo Wenlei , Fang Jian , Zhao Hui , Lin Zhong , Hu Yanping , Li Yarong , Zhang Shuqun , Cui Jiuwei , Kovalenko Nadezhda , Arslan Cagatay , Cabuk Devrim , Türker Alev , Bondarenko Igor , Hotko Yevhen , Goloborodko Olexandr , Chen Dongji , Wang Mengzhao , Yu Zhuang , Lu Junguo , Jiang Liyan , Xiong Hao , Giorgadze Davit , Orlov Sergey , Bilici Ahmet , Sinelnikov Ivan , Chen Gongyan , Yue Lu , Zhu Xiaoli , Lu Liqin , Zhvania Mariam , Ulanska Malgorzata , Lifirenko Igor , Andabekov Timur , Smagina Maria , Moiseenko Fedor , Urun Yuksel , Nie Ligong , Cao Bangwei , You Zhenyu , Huang Haixin , Ying Shenpeng , Tavartkiladze Alexandre , Kitiashvili Tariel , Matitashvili Amiran , Kortua Tsira , Kulikov Eugeny , Cheporov Sergey , Shirinkin Vadim , Ozguroglu Mustafa , Artac Mehmet , Kolesnik Oleksii , Gardashnikov Andrii , Pominchuk Denys 
Published: September 2022

ImportanceProgrammed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC.ObjectiveTo evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC.Design, Setting, and ParticipantsThis international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021.InterventionsPatients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks.Main Outcomes and MeasuresThe primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P &amp;lt; .012). There were 13 secondary outcomes, including progression-free survival and adverse events.ResultsAmong the 585 patients who were randomized (mean age, 61.1 [SD, 8.67] years; 104 [17.8%] women), 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment. All patients received study treatment and were included in the primary analyses. As of the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2-24.8 months). The median overall survival was significantly longer in the serplulimab group (15.4 months [95% CI, 13.3 months-not evaluable]) than in the placebo group (10.9 months [95% CI, 10.0-14.3 months]) (hazard ratio, 0.63 [95% CI, 0.49-0.82]; P &amp;lt; .001). The median progression-free survival (assessed by an independent radiology review committee) also was longer in the serplulimab group (5.7 months [95% CI, 5.5-6.9 months]) than in the placebo group (4.3 months [95% CI, 4.2-4.5 months]) (hazard ratio, 0.48 [95% CI, 0.38-0.59]). Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group.Conclusions and RelevanceAmong patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population.Trial RegistrationClinicalTrials.gov Identifier: NCT04063163