ImportanceImmune checkpoint inhibitor (ICI) plus chemotherapy combination treatment (ICI-chemotherapy) is now a standard treatment for non–small cell lung cancer (NSCLC) without targetable oncogene alterations, but there are few data on ICI-chemotherapy for patients 75 years and older.ObjectiveTo inform the choice of first-line drugs in clinical practice and assess the safety and efficacy of ICI-chemotherapy combination treatment in older adult patients with previously untreated advanced NSCLC.Design, Setting, and ParticipantsThis retrospective cohort study included 58 centers in Japan. The cohort consisted of patients 75 years and older with clinical stage IIIB, IIIC, IV, postoperative or radiotherapy recurrent NSCLC. Patients started first-line systemic therapy between December 2018 and March 2021. Those receiving first-line molecular targeted drugs were excluded. The data were analyzed from February 2022 to October 2022.ExposuresSystemic therapy.Main Outcomes and MeasuresThe main outcomes were overall survival (OS), progression-free survival (PFS), and safety.ResultsA total of 1245 patients (median [range] age, 78 [75-95] years; 967 [78%] male) with NSCLC were included in the cohort. Programmed death ligand–1 (PD-L1) expression of less than 1% occurred in 268 tumors (22%); 1% to 49% in 387 tumors (31%); 50% and higher in 410 tumors (33%), and unknown expression in 180 tumors (14%). Median OS was 20.0 (95% CI, 17.1-23.6) months for the 354 patients receiving ICI-chemotherapy (28%); 19.8 (95% CI, 16.5-23.8) months for the 425 patients receiving ICI alone (34%); 12.8 (95% CI, 10.7-15.6) months for the 311 patients receiving platinum-doublet chemotherapy (25%); and 9.5 (95% CI, 7.4-13.4) months for the 155 patients receiving single-agent chemotherapy (12%). After propensity score matching, no differences in OS and PFS were found between the patients receiving ICI-chemotherapy vs ICI alone. Each group consisted of 118 patients. For PD-L1 expression of 1% and higher the OS hazard ratio (HR) was 0.98 (95% CI, 0.67-1.42; P = .90), and the PFS HR was 0.92 (95% CI, 0.67-1.25; P = .59). Significance was also not reached when separately analyzed for lower or higher PD-L1 expression (1%-49% or ≥50%). However, grade 3 or higher immune-related adverse events occurred in 86 patients (24.3%) treated with ICI-chemotherapy and 76 (17.9%) with ICI alone (P = .03).Conclusions and RelevanceIn this study, ICI-chemotherapy combination treatment did not improve survival and increased the incidence of grade 3 and higher immune-related adverse events compared with ICI alone in patients 75 years and older. Based on these results, ICI alone may be recommended for older adult patients with PD-L1–positive NSCLC.

中文翻译：

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老年晚期非小细胞肺癌的免疫治疗或化学免疫治疗

重要性免疫检查点抑制剂（ICI）加化疗联合治疗（ICI化疗）现已成为无靶向癌基因改变的非小细胞肺癌（NSCLC）的标准治疗方法，但针对75岁及以上患者的ICI化疗数据很少目的为临床实践中一线药物的选择提供信息，并评估 ICI-化疗联合治疗对既往未经治疗的晚期 NSCLC 老年患者的安全性和有效性。设计、背景和参与者这项回顾性队列研究包括日本 58 个中心。该队列由 75 岁及以上临床 IIIB、IIIC、IV 期、术后或放疗复发 NSCLC 患者组成。患者于2018年12月至2021年3月期间开始一线全身治疗。接受一线分子靶向药物的患者被排除。数据分析时间为2022年2月至2022年10月。暴露系统治疗。主要结果和措施主要结果为总生存期（OS）、无进展生存期（PFS）和安全性。结果共有1245名患者（中位[范围]年龄，该队列中包括 78 [75-95] 岁；967 [78%] 男性）患有 NSCLC 的患者。268 个肿瘤 (22%) 中出现程序性死亡配体-1 (PD-L1) 表达低于 1%；387 个肿瘤中为 1% 至 49% (31%)；在 410 个肿瘤 (33%) 中表达为 50% 或更高，在 180 个肿瘤 (14%) 中表达未知。354 名接受 ICI 化疗的患者 (28%) 的中位 OS 为 20.0 (95% CI, 17.1-23.6) 个月；425 名单独接受 ICI 的患者 (34%) 为 19.8 (95% CI, 16.5-23.8) 个月；311 名接受铂类双药化疗的患者 (25%) 为 12.8 (95% CI, 10.7-15.6) 个月；155 名接受单药化疗的患者 (12%) 为 9.5 个月 (95% CI，7.4-13.4) 个月。倾向评分匹配后，接受 ICI 化疗的患者与单独 ICI 的患者之间没有发现 OS 和 PFS 差异。每组由 118 名患者组成。对于 1% 及更高的 PD-L1 表达，OS 风险比 (HR) 为 0.98（95% CI，0.67-1.42；磷= .90），PFS HR 为 0.92（95% CI，0.67-1.25；磷= .59）。当单独分析较低或较高的 PD-L1 表达（1%-49% 或≥50%）时，也未达到显着性。然而，接受 ICI 化疗的 86 名患者（24.3%）和仅接受 ICI 治疗的 76 名患者（17.9%）发生了 3 级或以上的免疫相关不良事件。磷= .03)。结论和相关性在这项研究中，与单独使用 ICI 相比，ICI 联合化疗并不能提高 75 岁及以上患者的生存率，并且会增加 3 级及以上免疫相关不良事件的发生率。基于这些结果，可能建议 PD-L1 阳性 NSCLC 老年患者单独使用 ICI。