Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial.

Autor:	Cheng Y; Department of Oncology, Jilin Cancer Hospital, Changchun, China., Han L; Department of Oncology, Xuzhou Central Hospital, Xuzhou, China., Wu L; Department of Thoracic Medical Oncology, Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China., Chen J; Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China., Sun H; Department of Oncology, Jiamusi Cancer Hospital, Jiamusi, China., Wen G; Department of Respiratory Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, China., Ji Y; Department of Oncology, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China., Dvorkin M; Budgetary Healthcare Institution of Omsk Region Clinical Oncology Dispensary, Omsk, Russia., Shi J; Department of Oncology, Linyi Cancer Hospital, Linyi, China., Pan Z; Department of Respiratory Medicine, the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China., Shi J; Department of Oncology, Cangzhou People's Hospital, Changchun, China., Wang X; Department of Oncology, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China., Bai Y; Department of Oncology and Hematology, China-Japan Union Hospital of Jilin University, Changchun, China., Melkadze T; Academician Fridon Todua Medical Center-Research Institute of Clinical Medicine, Tbilisi, Georgia., Pan Y; Department of Oncology, Anhui Provincial Hospital, Hefei, China., Min X; Department of Interventional Radiology, Anhui Chest Hospital, Hefei, China., Viguro M; Clinical Research Department, Medical Center Mriya Med-Service, Kryvyi Rih, Ukraine., Li X; Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Zhao Y; Department of Medical Oncology, the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China., Yang J; Department of Oncology, Tangshan People's Hospital, Tangshan, China., Makharadze T; Department of Oncology-Endocrinology, High Technology Hospital MedCenter LTD, Batumi, Georgia., Arkania E; LTD Israeli-Georgian Medical Research Clinic Helsicore, Tbilisi, Georgia., Kang W; Shanghai Henlius Biotech, Inc, Shanghai, China., Wang Q; Shanghai Henlius Biotech, Inc, Shanghai, China., Zhu J; Shanghai Henlius Biotech, Inc, Shanghai, China.
Jazyk:	angličtina
Zdroj:	JAMA [JAMA] 2022 Sep 27; Vol. 328 (12), pp. 1223-1232.
DOI:	10.1001/jama.2022.16464
Abstrakt:	Importance: Programmed 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. Objective: To 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 Participants: This 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. Interventions: Patients 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 Measures: The primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P < .012). There were 13 secondary outcomes, including progression-free survival and adverse events. Results: Among 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 < .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 Relevance: Among 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 Registration: ClinicalTrials.gov Identifier: NCT04063163.
Databáze:	MEDLINE
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