多西紫杉醇
医学
无容量
内科学
肿瘤科
肺癌
危险系数
化疗
临床研究阶段
无进展生存期
癌症
临床终点
置信区间
随机对照试验
免疫疗法
作者
Hossein Borghaei,Filippo de Marinis,Daphne W. Dumoulin,Craig H. Reynolds,Willemijn S.M.E. Theelen,Ivor Percent,V. Gutiérrez Calderón,Melissa L. Johnson,A. Madroszyk-Flandin,Edward B. Garon,Kaitlyn He,David Planchard,Martin Reck,Sanjay Popat,Roy S. Herbst,Ticiana Leal,Ronald Shazer,Xin Yan,Richard Harrigan,Solange Peters
标识
DOI:10.1016/j.annonc.2023.10.004
摘要
Checkpoint inhibitor (CPI) therapy revolutionized treatment for advanced non-small-cell lung cancer (NSCLC); however, most patients progress due to primary or acquired resistance. Sitravatinib is a receptor tyrosine kinase inhibitor that can shift the immunosuppressive tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with nivolumab (sitra + nivo) may potentially overcome initial CPI resistance.In the phase III SAPPHIRE study, patients with advanced non-oncogenic driven, nonsquamous NSCLC who initially benefited from (≥4 months on CPI without progression) and subsequently experienced disease progression on or after CPI combined with or following platinum-based chemotherapy were randomized 1 : 1 to sitra (100 mg once daily administered orally) + nivo (240 mg every 2 weeks or 480 mg every 4 weeks administered intravenously) or docetaxel (75 mg/m2 every 3 weeks administered intravenously). The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR; all assessed by blinded independent central review), and safety.A total of 577 patients included randomized: sitra + nivo, n = 284; docetaxel, n = 293 (median follow-up, 17.1 months). Sitra + nivo did not significantly improve OS versus docetaxel [median, 12.2 versus 10.6 months; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.70-1.05; P = 0.144]. The median PFS was 4.4 versus 5.4 months, respectively (HR 1.08, 95% CI 0.89-1.32; P = 0.452). The ORR was 15.6% for sitra + nivo and 17.2% for docetaxel (P = 0.597); CBR was 75.5% and 64.5%, respectively (P = 0.004); median DOR was 7.4 versus 7.1 months, respectively (P = 0.924). Grade ≥3 treatment-related adverse events were observed in 53.0% versus 66.7% of patients receiving sitra + nivo versus docetaxel, respectively.Although median OS was numerically longer with sitra + nivo, the primary endpoint was not met in patients with previously treated advanced nonsquamous NSCLC. The safety profiles demonstrated were consistent with previous reports.
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