Background: The long overall survival (OS) observed among patients with non-small cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression in chemoimmunotherapy (CIT) groups in previous phase III trials suggests the limited efficacy of CIT among the subgroup with ≤49% PD-L1 expression on tumor cells. Hence, sequential treatment with first-line platinum-based chemotherapy followed by second-line immune checkpoint inhibitor treatment (SEQ) is an option. This study examined whether first-line CIT would provide better outcomes than SEQ in patients with advanced NSCLC with ≤49% PD-L1 expression. Methods: This retrospective study evaluated patients with untreated NSCLC who received first-line CIT or SEQ at nine hospitals in Japan. OS, progression-free survival (PFS), PFS-2 (the time from first-line treatment to progression to second-line treatment or death), and other related outcomes were evaluated between the CIT and SEQ groups. Results: Among the 305 enrolled patients, 234 eligible patients were analyzed: 165 in the CIT group and 69 in the SEQ group. The COX proportional hazards model suggested a significant interaction between PD-L1 expression and OS (p= 0.006). OS in the CIT group was significantly longer than that in the SEQ group in the 1–49% PD-L1 expression subgroup but not in the <1% PD-L1 expression subgroup. Among the subgroup with 1–49% PD-L1 expression, the CIT group exhibited longer median PFS than the SEQ group (CIT: 9.3 months (95% CI: 6.7–14.8) vs. SEQ:5.5 months (95% CI: 4.5–6.1);p< 0.001), while the median PFS in the CIT group was not statistically longer than the median PFS-2 in the SEQ group (p= 0.586). There was no significant difference between the median PFS in the CIT and SEQ groups among the <1% PD-L1 expression subgroup (p= 0.883); the median PFS-2 in the SEQ group was significantly longer than the median PFS in the CIT group (10.5 months (95% CI: 5.9–15.3) vs. 6.4 months (95% CI: 4.9–7.5);p= 0.024). Conclusions: CIT is recommended for patients with NSCLC with 1–49% PD-L1 expression because it significantly improved OS and PFS compared to SEQ. CIT had limited benefits in patients with <1% PD-L1 expression, and the median PFS-2 in the SEQ group was significantly longer than the median PFS in the CIT group. These findings will help physicians select the most suitable treatment option for patients with NSCLC, considering PD-L1 expressions.
背景：既往III期试验中，化疗免疫联合治疗组中程序性死亡配体1高表达的非小细胞肺癌患者观察到较长的总生存期，提示该疗法在肿瘤细胞PD-L1表达≤49%亚组中的疗效有限。因此，一线含铂化疗序贯二线免疫检查点抑制剂治疗可作为备选方案。本研究旨在探讨对于PD-L1表达≤49%的晚期NSCLC患者，一线化疗免疫联合治疗是否较序贯治疗能带来更佳预后。方法：本回顾性研究纳入日本九家医院收治的初治NSCLC患者，评估接受一线化疗免疫联合治疗或序贯治疗患者的预后差异。比较两组患者的总生存期、无进展生存期、二线治疗无进展生存期及其他相关结局指标。结果：在305例入组患者中，最终对234例符合条件者进行分析：化疗免疫联合治疗组165例，序贯治疗组69例。COX比例风险模型显示PD-L1表达水平与总生存期存在显著交互作用。在PD-L1表达1-49%亚组中，化疗免疫联合治疗组总生存期显著优于序贯治疗组，而在PD-L1表达<1%亚组中未见显著差异。在PD-L1表达1-49%亚组中，化疗免疫联合治疗组中位无进展生存期显著长于序贯治疗组，但未显著优于序贯治疗组的中位二线治疗无进展生存期。在PD-L1表达<1%亚组中，两组中位无进展生存期无显著差异，而序贯治疗组的中位二线治疗无进展生存期显著优于化疗免疫联合治疗组的中位无进展生存期。结论：对于PD-L1表达1-49%的NSCLC患者，推荐采用化疗免疫联合治疗方案，因其较序贯治疗能显著改善总生存期和无进展生存期。对于PD-L1表达<1%的患者，化疗免疫联合治疗获益有限，且序贯治疗组的中位二线治疗无进展生存期显著优于化疗免疫联合治疗组的中位无进展生存期。这些发现将有助于临床医生根据PD-L1表达水平为NSCLC患者选择最适宜的治疗方案。
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