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一线免疫检查点抑制剂联合化疗治疗广泛期小细胞肺癌的疗效和安全性:一项网状Meta分析。

Efficacy and safety of first-line immune checkpoint inhibitors combined with chemotherapy for extensive-stage small cell lung cancer: A network meta-analysis.

作者信息

Wang Shuxing, Li Yunshu, Liu Zhuqing, Tian Wentao, Zeng Yue, Liu Junqi, Zhang Sujuan, Peng Yurong, Wu Fang

机构信息

Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Xiangya School of Medicine, Central South University, Changsha 410078, Hunan, China.

Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.

出版信息

Lung Cancer. 2023 Apr;178:47-56. doi: 10.1016/j.lungcan.2023.02.003. Epub 2023 Feb 4.

Abstract

The efficacy and safety of first-line immune checkpoint inhibitors plus chemotherapy in the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) remains unevaluated, and there are no reports to directly compare the efficacy and safety among different immunotherapy (especially adebrelimab and surplulimab). Suitable phase III randomized controlled trials with two or more different arms were included. Independent reviewers screened and extracted relevant data and disagreements were resolved through consensus. Fixed-effect consistency models were used to calculate the overall survival (OS), progression-free survival (PFS), objective response rate, adverse events ≥ 3, and safety outcomes in the clinically relevant subgroups. In this network meta-analysis, six randomized controlled clinical trials (CAPSTONE-1, ASTRUM-005, CASPIAN, IMpower133, KEYNOTE-604, and an ipilimumab + chemotherapy trial) with totaling 3662 patients were involved. Compared to chemotherapy, immune checkpoint inhibitors plus chemotherapy present higher possibilities to bring about better OS and PFS. Serplulimab + chemotherapy significantly showed a better survival profit in comparison with ipilimumab + chemotherapy (0.67; 0.50-0.90). Compared with chemotherapy, adebrelimab + chemotherapy (0.72; 0,58-0.90), atezolizumab + chemotherapy (0.76; 0.60-0.96) durvalumab + chemotherapy (0.75; 0.62-0.91), and serplulimab + chemotherapy (0.63;0.49-0.82) all presented significantly better overall survival. In terms of progression-free survival, serplulimab + chemotherapy showed better efficacy in comparison with adebrelimab + chemotherapy (0.72; 0,53-0.97), atezolizumab + chemotherapy (0.62; 0.46-0.84), durvalumab + chemotherapy (0.60; 0.45-0.80). Compared with chemotherapy, adebrelimab + chemotherapy (0.67; 0.54-0.83) and serplulimab + chemotherapy (0.48; 0.48-0.86) all presented significantly better PFS. Immunotherapy plus chemotherapy had similar probabilities to cause adverse events of grade ≥ 3. In comparison with chemotherapy, immune checkpoint inhibitors plus chemotherapy were likely to be more suitable for the first-line treatment of ES-SCLC. According to our analysis, serplulimab plus chemotherapy and adebrelimab plus chemotherapy present higher possibilities to show better efficacy and safety, however, the level of evidence of this type of comparison is limited.

摘要

一线免疫检查点抑制剂联合化疗治疗广泛期小细胞肺癌(ES-SCLC)患者的疗效和安全性尚未得到评估,也没有直接比较不同免疫疗法(尤其是阿得贝利单抗和斯鲁利单抗)疗效和安全性的报告。纳入了合适的具有两个或更多不同治疗组的III期随机对照试验。独立评审员筛选并提取相关数据,分歧通过协商一致解决。使用固定效应一致性模型计算总生存期(OS)、无进展生存期(PFS)、客观缓解率、≥3级不良事件以及临床相关亚组的安全性结果。在这项网络荟萃分析中,涉及6项随机对照临床试验(CAPSTONE-1、ASTRUM-005、CASPIAN、IMpower133、KEYNOTE-604以及一项伊匹木单抗联合化疗试验),共计3662例患者。与化疗相比,免疫检查点抑制剂联合化疗更有可能带来更好的OS和PFS。与伊匹木单抗联合化疗相比,斯鲁利单抗联合化疗显著显示出更好的生存获益(0.67;0.50-0.90)。与化疗相比,阿得贝利单抗联合化疗(0.72;0.58-0.90)、阿替利珠单抗联合化疗(0.76;0.60-0.96)、度伐利尤单抗联合化疗(0.75;0.62-0.91)以及斯鲁利单抗联合化疗(0.63;0.49-0.82)均显著显示出更好的总生存期。在无进展生存期方面,与阿得贝利单抗联合化疗(0.72;0.53-0.97)、阿替利珠单抗联合化疗(0.62;0.46-0.84)、度伐利尤单抗联合化疗(0.60;0.45-0.80)相比,斯鲁利单抗联合化疗显示出更好的疗效。与化疗相比,阿得贝利单抗联合化疗(0.67;0.54-0.83)和斯鲁利单抗联合化疗(0.48;0.48-0.86)均显著显示出更好的PFS。免疫疗法联合化疗导致≥3级不良事件的概率相似。与化疗相比,免疫检查点抑制剂联合化疗可能更适合ES-SCLC的一线治疗。根据我们的分析,斯鲁利单抗联合化疗和阿得贝利单抗联合化疗更有可能显示出更好的疗效和安全性,然而,这类比较的证据水平有限。

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