Department of Medical Oncology, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
Department of Clinical Laboratory, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
JAMA Netw Open. 2020 Oct 1;3(10):e2015748. doi: 10.1001/jamanetworkopen.2020.15748.
Combinations of chemotherapy with immunotherapy or bevacizumab in first-line treatments of extensive-stage small cell lung cancer (ES-SCLC) have been evaluated in various clinical trials. However, it remains unclear what the optimal combination regimen is.
To clarify which first-line combination regimen is associated with the best tumor response among patients with ES-SCLC.
Electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were systematically searched to extract eligible literature from database inception to December 2019.
Head-to-head randomized clinical trials on first-line treatments for patients with ES-SCLC were included with outcomes and toxic effects reported, including objective response rate (ORR, involving complete response and partial response), disease control rate (DCR, involving complete response, partial response, and stable disease), progression-free survival (PFS), overall survival (OS), and treatment related adverse events (TRAEs) of grades 3 to 5. Of 199 eligible articles, 14 were included.
Data were independently extracted and collected by 2 reviewers based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Data were pooled using a random-effects model.
Main outcomes were OS, PFS, DCR, ORR, and TRAEs of grades 3 to 5.
A total of 3 phase 2 and 11 phase 3 randomized clinical trials involving 4838 patients were included. Programmed cell death ligand 1 (PD-L1) inhibitor (durvalumab and atezolizumab) plus etoposide-based chemotherapy, compared with etoposide-based chemotherapy alone, showed the most favorable OS (hazard ratio, 1.40; 95% CI, 1.09-1.80) and the best DCR (odds ratio [OR], 0.42; 95% CI, 0.21-0.81). Bevacizumab plus etoposide-based chemotherapy provided the best PFS compared with etoposide-based chemotherapy alone (hazard ratio, 1.54; 95% CI, 1.09-2.27), although this was not translated into OS benefit. The addition of PD-L1 inhibitors to etoposide-platinum chemotherapy caused no more toxic effects in general (compared with etoposide-based chemotherapy alone: OR, 1.14; 95% CI, 0.36-2.31), while bevacizumab plus etoposide-platinum regimen induced the most TRAEs grades 3 to 5 among all first-line treatments (eg, compared with irinotecan-platinum regimen: OR, 4.24; 95% CI, 1.26-14.57). Based on the surface under the cumulative ranking curve value, PD-L1 inhibitor plus etoposide-platinum had the highest probability of being ranked first for OS (0.87) and DCR (0.97).
The findings of this systematic review and network meta-analysis suggest that the combination of a PD-L1 inhibitor (durvalumab and atezolizumab) and etoposide-based chemotherapy may be an optimal first-line treatment option for patients with ES-SCLC patients.
在广泛期小细胞肺癌（ES-SCLC）的一线治疗中，化疗联合免疫疗法或贝伐珠单抗的组合已在各种临床试验中进行了评估。然而，目前仍不清楚哪种联合方案是最佳的。
明确在 ES-SCLC 患者中，哪种一线联合方案与最佳肿瘤反应相关。
系统检索电子数据库（PubMed、Embase、Cochrane 对照试验中心注册库和 Web of Science），以提取从数据库成立到 2019 年 12 月的合格文献。
纳入了头对头随机临床试验，这些试验涉及 ES-SCLC 患者的一线治疗，报告了结局和毒性效应，包括客观缓解率（ORR，包括完全缓解和部分缓解）、疾病控制率（DCR，包括完全缓解、部分缓解和稳定疾病）、无进展生存期（PFS）、总生存期（OS）和治疗相关的 3 至 5 级不良事件（TRAEs）。在 199 篇合格文章中，有 14 篇被纳入。
两位评审员根据系统评价和荟萃分析的首选报告项目（PRISMA）指南独立提取和收集数据。使用随机效应模型对数据进行汇总。
主要结局为 OS、PFS、DCR、ORR 和 3 至 5 级 TRAEs。
共纳入 3 项 2 期和 11 项 3 期随机临床试验，涉及 4838 例患者。程序性死亡配体 1（PD-L1）抑制剂（度伐利尤单抗和阿替利珠单抗）联合依托泊苷为基础的化疗与依托泊苷为基础的化疗相比，具有最有利的 OS（风险比，1.40；95%置信区间，1.09-1.80）和最佳的 DCR（比值比 [OR]，0.42；95%置信区间，0.21-0.81）。贝伐珠单抗联合依托泊苷为基础的化疗与依托泊苷为基础的化疗相比，可提供最佳的 PFS（风险比，1.54；95%置信区间，1.09-2.27），尽管这并未转化为 OS 获益。PD-L1 抑制剂联合依托泊苷-铂类化疗通常不会增加更多的毒性效应（与依托泊苷为基础的化疗相比：OR，1.14；95%置信区间，0.36-2.31），而贝伐珠单抗联合依托泊苷-铂类方案在所有一线治疗中引起的 3 至 5 级 TRAEs 最多（例如，与伊立替康-铂类方案相比：OR，4.24；95%置信区间，1.26-14.57）。基于累积排序曲线下面积值，PD-L1 抑制剂联合依托泊苷-铂类方案在 OS（0.87）和 DCR（0.97）方面具有最高的排名第一的可能性。
这项系统评价和网络荟萃分析的结果表明，PD-L1 抑制剂（度伐利尤单抗和阿替利珠单抗）联合依托泊苷为基础的化疗可能是 ES-SCLC 患者的最佳一线治疗选择。
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