Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Front Immunol. 2022 Apr 5;13:764643. doi: 10.3389/fimmu.2022.764643. eCollection 2022.
Immune checkpoint inhibitors (ICIs) have significantly improved survival for advanced wild-type non-small cell lung cancer, but there is no direct comparison to confirm which first-line treatment may lead to the longest overall survival. What qualifies as long-term survival (LS) is even unclear.
By searching PubMed, Embase, and the Cochrane Central Register of Controlled Trials from January 2005 to December 2020, we included randomized controlled trials (RCTs) of first-line ICI-containing treatments to perform an integrated analysis (IA) to determine the criterion of LS and then screened regimens with LS for network meta-analysis (NMA). The main outcomes for NMA were median overall survival (mOS), 1-year survival rate (1ySR), and 2-year survival rate (2ySR); those for IA were the pooled mOS (POS), 1ySR (P1SR), and 2ySR (P2SR).
By IA of 16 first-line ICIs from 20 RCTs, the POS was 16.20 (95% CI 14.79-17.60) months, with P1SR of 63% (95% CI 59-66%) and P2SR of 37% (33-41%). Thus, we defined LS as mOS ≥ POS (16.20 m) for regimens and screened for RCTs with outcomes meeting this criterion. Eleven ICI-based regimens can bring LS for the overall population, among which ICI with bevacizumab and chemotherapy achieved the longest POS of 19.50 m (16.90-22.10 m) and the highest P1SR (74%, 61%-87%) and P2SR (49%, 38%-61%). Pembrolizumab with chemotherapy ranked first in mOS and 1ySR, while atezolizumab plus bevacizumab and chemotherapy ranked first in 2ySR.
Through the IA of first-line treatment regimens, a POS of 16.20 m can be determined as the LS standard. Further considering 1ySR and 2ySR, atezolizumab combined with bevacizumab and chemotherapy or pembrolizumab plus chemotherapy are likely to bring the longest LS in the overall population, while single ICI may be adequate for patients with a high PD-L1 expression. ICIs with bevacizumab and chemotherapy may be the best combination for LS for its further advantage over time.
免疫检查点抑制剂（ICIs）显著提高了晚期野生型非小细胞肺癌的生存率，但尚无直接比较来确认哪种一线治疗可能带来最长的总生存期。何为长期生存（LS）甚至都不明确。
通过检索 2005 年 1 月至 2020 年 12 月期间的 PubMed、Embase 和 Cochrane 中央对照试验注册库，我们纳入了一线含 ICI 的治疗方案的随机对照试验（RCT），以进行综合分析（IA）来确定 LS 的标准，然后筛选 LS 方案进行网络荟萃分析（NMA）。NMA 的主要结局指标是中位总生存期（mOS）、1 年生存率（1ySR）和 2 年生存率（2ySR）；IA 的主要结局指标是汇总的 mOS（POS）、1 年生存率（P1SR）和 2 年生存率（P2SR）。
通过对 20 项 RCT 中 16 种一线 ICIs 的 IA 分析，POS 为 16.20 个月（95%CI 14.79-17.60），1 年生存率（P1SR）为 63%（95%CI 59-66%），2 年生存率（P2SR）为 37%（33-41%）。因此，我们将 LS 定义为方案的 mOS≥POS（16.20 m），并筛选符合该标准的 RCT 结果。11 种基于 ICI 的方案可使总体人群获得 LS，其中 ICI 联合贝伐珠单抗和化疗的 POS 最长，为 19.50 个月（16.90-22.10 个月），1 年生存率（P1SR）最高（74%，61%-87%），2 年生存率（P2SR）最高（49%，38%-61%）。化疗联合培美曲塞的方案在 mOS 和 1 年生存率方面排名第一，而化疗联合阿替利珠单抗和贝伐珠单抗的方案在 2 年生存率方面排名第一。
通过一线治疗方案的 IA，可以确定 16.20 个月的 POS 作为 LS 标准。进一步考虑 1 年生存率和 2 年生存率，阿替利珠单抗联合贝伐珠单抗和化疗或帕博利珠单抗联合化疗可能在总体人群中带来最长的 LS，而单药 ICI 可能足以满足 PD-L1 高表达患者的需求。ICI 联合贝伐珠单抗和化疗可能是 LS 的最佳组合，因为随着时间的推移它具有进一步的优势。
