Department of Respiratory Medicine, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
School of Health, Brooks College (Sunnyvale), Sunnyvale, CA, United States.
Front Immunol. 2023 Jun 26;14:1197044. doi: 10.3389/fimmu.2023.1197044. eCollection 2023.
Despite numerous immunotherapy and chemotherapy regimens available for patients with extensive-stage small cell lung cancer (ES-SCLC), it remains unclear which regimen is the most effective and safest; relative studies comparing such regimens are scarce.
The aim of this study was to investigate the efficacy and safety of first-line immunotherapy combinations with chemotherapy for patients with extensive-stage small cell lung cancer. In addition, for the first time, comparisons among the first-line systemic regimens on OS and PFS in ES-SCLC by each time node were made.
Databases including PubMed, Embase, Cochrane Library, Scopus, Google Scholars, and ClinicalTrials.gov, and major international conferences were searched for randomized controlled trials (RCTs) regarding comparing immunotherapy combinations with chemotherapy as first-line treatments for patients with advanced ES-SCLC from inception to 1 November. Hazard ratios (HRs) and odds ratios (ORs) were generated for dichotomous variants by RStudio 4.2.1. The outcomes comprised overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events of grade 3 or higher (Grade ≥ 3 AEs).
Eventually, a total of nine RCTs reporting 4,352 individuals with nine regimens were enrolled. The regimens were ipilimumabnu (Ipi), atezolizumab (Atez), durvalumab plus tremelimumab (Durv-Trem), durvalumab (Durv), pembrolizumab (Pemb), adebrelimab (Adeb), serplulimab (Serp), atezolizumab plus tiragolumab (Atez-Tira), and nivolumab (Nivo). With regard to OS, serplulimab (HR = 0.63, 95% CI: 0.49 to 0.81) was found to yield the best OS benefit when compared with chemotherapy. Meanwhile, serplulimab had the highest probability (46.11%) for better OS. Furthermore, compared with chemotherapy, serplulimab significantly increased the OS rate from the 6th to the 21st month. With regard to PFS, serplulimab (HR = 0.47, 95% CI: 0.38 to 0.59) was found to yield the best PFS benefit when compared with chemotherapy. Simultaneously, serplulimab had the highest probability (94.48%) for better PFS. Serplulimab was also a long-lasting first-line regimen in both OS and PFS from a longitudinal perspective. In addition, there was no significant difference among the various treatment options for ORR and grade ≥3 AEs.
Considering OS, PFS, ORR, and safety profiles, serplulimab with chemotherapy should be recommended as the best therapy for patients with ES-SCLC. Certainly, more head-to-head studies are needed to confirm these findings.
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022373291.
尽管有许多免疫疗法和化疗方案可用于广泛期小细胞肺癌（ES-SCLC）患者，但哪种方案最有效和最安全仍不清楚；相对的比较这些方案的研究很少。
本研究旨在探讨一线免疫联合化疗治疗广泛期小细胞肺癌的疗效和安全性。此外，首次按每个时间节点比较 ES-SCLC 一线系统方案在 OS 和 PFS 上的比较。
检索了 PubMed、Embase、Cochrane 图书馆、Scopus、Google Scholar 和 ClinicalTrials.gov 等数据库，以及主要的国际会议，以检索自成立以来至 2023 年 11 月 1 日比较免疫联合化疗作为晚期 ES-SCLC 患者一线治疗的随机对照试验（RCT）。使用 RStudio 4.2.1 为二分类变量生成风险比（HR）和优势比（OR）。结果包括总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和 3 级或以上不良事件（Grade≥3 AEs）。
最终，共有 9 项 RCT 纳入了 4352 名接受 9 种方案治疗的患者。这些方案是 ipilimumabnu（Ipi）、atezolizumab（Atez）、durvalumab 加 tremelimumab（Durv-Trem）、durvalumab（Durv）、pembrolizumab（Pemb）、adebrelimab（Adeb）、serplulimab（Serp）、atezolizumab 加 tiragolumab（Atez-Tira）和 nivolumab（Nivo）。在 OS 方面，与化疗相比，serplulimab（HR=0.63，95%CI：0.49 至 0.81）被发现具有最佳的 OS 获益。同时，serplulimab 具有最佳 OS 获益的概率最高（46.11%）。此外，与化疗相比，serplulimab 从第 6 个月到第 21 个月显著增加了 OS 率。在 PFS 方面，与化疗相比，serplulimab（HR=0.47，95%CI：0.38 至 0.59）被发现具有最佳的 PFS 获益。同时，serplulimab 具有最佳 PFS 获益的概率最高（94.48%）。从纵向角度来看，serplulimab 也是一种在 OS 和 PFS 方面都持久的一线方案。此外，在 ORR 和 Grade≥3 AEs 方面，各种治疗方案之间没有显著差异。
考虑到 OS、PFS、ORR 和安全性，serplulimab 联合化疗应该被推荐为 ES-SCLC 患者的最佳治疗方案。当然，还需要更多的头对头研究来证实这些发现。
https://www.crd.york.ac.uk/PROSPERO/，标识符 CRD42022373291。
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