Cancer Medicine Department, Gustave Roussy, Villejuif, France; Medical Oncology Department, Cochin Hospital, Paris, France.
Cancer Medicine Department, Gustave Roussy, Villejuif, France; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Barcelona, Spain.
Eur J Cancer. 2021 Mar;145:221-229. doi: 10.1016/j.ejca.2020.10.017. Epub 2021 Jan 27.
The established role of morphological evaluation of tumour-infiltrating lymphocytes (TILs) with immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) is unknown. We aimed to determine TIL association with the outcome for ICIs and for chemotherapy in advanced NSCLC.
This is a multicenter retrospective study of a nivolumab cohort of 221 patients treated between November 2012 and February 2017 and a chemotherapy cohort of 189 patients treated between June 2009 and October 2016. Patients with available tissue for stromal TIL evaluation were analysed. The presence of a high TIL count (high-TIL) was defined as ≥10% density. The primary end-point was overall survival (OS).
Among the nivolumab cohort, 64% were male, with median age of 63 years, 82.3% were smokers, 77% had performance status ≤1 and 63% had adenocarcinoma histology. High-TIL was observed in 22% patients and associated with OS (hazard ratio [HR] 0.48; 95% confidence interval [95% CI]: 0.28-0.81) and progression-free survival [PFS] (HR = 0.40; 95% CI: 0.25-0.64). Median PFS was 13.0 months (95% CI: 5.0-not reached) with high-TIL versus 2.2 months (95% CI: 1.7-3.0) with the presence of a low TIL count (low-TIL). Median OS for high-TIL was not reached (95% CI: 12.2-not reached) versus 8.4 months (95% CI: 5.0-11.6) in the low-TIL group. High-TIL was associated with the overall response rate (ORR) and disease control rate (DCR) (both, P < .0001). Among the chemotherapy cohort, 69% were male, 89% were smokers, 86% had performance status ≤1 and 90% had adenocarcinoma histology. High-TIL was seen in 37%. Median PFS and OS were 5.7 months (95% CI: 4.9-6.7) and 11.7 months (95% CI: 9.3-13.0), respectively, with no association with TILs.
High-TIL was associated with favourable outcomes in a real-world immunotherapy cohort of patients with NSCLC, but not with chemotherapy, suggesting that TILs may be useful in selecting patients for immunotherapy.
免疫检查点抑制剂（ICI）在非小细胞肺癌（NSCLC）中肿瘤浸润淋巴细胞（TILs）形态评估的既定作用尚不清楚。我们旨在确定 TIL 与 ICI 和晚期 NSCLC 化疗的结果之间的关联。
这是一项多中心回顾性研究，纳入了 2012 年 11 月至 2017 年 2 月接受纳武利尤单抗治疗的 221 例患者的纳武利尤单抗队列和 2009 年 6 月至 2016 年 10 月接受化疗的 189 例患者的化疗队列。分析了有组织学评估间质 TIL 数据的患者。高 TIL 计数（高-TIL）定义为密度≥10%。主要终点为总生存期（OS）。
纳武利尤单抗队列中，64%为男性，中位年龄 63 岁，82.3%为吸烟者，77%的体能状态评分为 1 分或以下，63%为腺癌组织学。22%的患者观察到高-TIL，并与 OS（风险比[HR]0.48；95%置信区间[95%CI]：0.28-0.81）和无进展生存期[PFS]（HR=0.40；95%CI：0.25-0.64）相关。高-TIL 患者的中位 PFS 为 13.0 个月（95%CI：5.0-无进展），低-TIL 患者为 2.2 个月（95%CI：1.7-3.0）。高-TIL 患者的中位 OS 无进展（95%CI：12.2-无进展），低-TIL 患者为 8.4 个月（95%CI：5.0-11.6）。高-TIL 与总缓解率（ORR）和疾病控制率（DCR）相关（均 P<0.0001）。化疗队列中，69%为男性，89%为吸烟者，86%的体能状态评分为 1 分或以下，90%为腺癌组织学。高-TIL 为 37%。中位 PFS 和 OS 分别为 5.7 个月（95%CI：4.9-6.7）和 11.7 个月（95%CI：9.3-13.0），与 TIL 无关。
在 NSCLC 的真实世界免疫治疗队列中，高-TIL 与有利的结果相关，但与化疗无关，提示 TIL 可能有助于选择免疫治疗患者。
