Department of Medical Oncology, Center Georges François Leclerc, 1 rue du Professeur Marion, 21000, Dijon, France.
Research Platform in Biological Oncology, Dijon, France.
J Cancer Res Clin Oncol. 2020 Oct;146(10):2699-2707. doi: 10.1007/s00432-020-03262-2. Epub 2020 May 30.
Checkpoint inhibitors (CKI) targeting PD-1 or PD-L1 are major therapies for the treatment of non-small cell lung cancer (NSCLC). Despite numerous studies of biological biomarkers, we currently lack a marker to predict CKI primary resistance. The aim of this study was to isolate clinical markers associated with the absence of efficacy of CKI used as monotherapy in NSCLC.
We conducted a retrospective analysis of 172 patients treated with anti-PD1 or anti-PDL1 monoclonal antibodies (mAb) for advanced NSCLC at the Dijon Cancer Center. Baseline characteristics were compared using the Chi squared test between responders and non-responders. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test for univariate analysis. Cox regression models were used to determine hazard ratios and 95% confidence intervals for progression-free survival (PFS) and overall survival (OS).
Among 172 patients included, 149 (86.5%) received CKI after platinum chemotherapy. Response rate (RR) was 16%, median progression-free survival (PFS) was 2.5 months (95% CI 0.7-30 months) and median overall survival (OS) was 10 months (95% CI 0.7-46.8 months). By univariate analysis, WHO performance status ≥ 1, presence of bone, liver and pleuroperitoneal metastasis were associated with poor PFS and OS. Multivariate analysis showed that only pleuroperitoneal metastasis was independently associated with PFS and OS. Patients with pleuroperitoneal metastasis and WHO performance status ≥ 1 had a < 10% chance of yielding a benefit from CKI.
Our data support the hypothesis that pleuroperitoneal metastasis is a major predictive factor affecting CKI efficacy in NSCLC patients and may be used to avoid CKI monotherapy for such patients.
针对 PD-1 或 PD-L1 的检查点抑制剂（CKI）是治疗非小细胞肺癌（NSCLC）的主要疗法。尽管有许多关于生物标志物的研究，但我们目前缺乏预测 CKI 原发性耐药的标志物。本研究旨在分离与 NSCLC 患者 CKI 单药治疗无效相关的临床标志物。
我们对在第戎癌症中心接受抗 PD-1 或抗 PD-L1 单克隆抗体（mAb）治疗晚期 NSCLC 的 172 名患者进行了回顾性分析。采用卡方检验比较应答者和无应答者之间的基线特征。通过 Kaplan-Meier 方法估计生存曲线，并通过对数秩检验进行单因素分析比较。Cox 回归模型用于确定无进展生存期（PFS）和总生存期（OS）的风险比和 95%置信区间。
在纳入的 172 名患者中，有 149 名（86.5%）在铂类化疗后接受了 CKI。客观缓解率（RR）为 16%，中位无进展生存期（PFS）为 2.5 个月（95%CI 0.7-30 个月），中位总生存期（OS）为 10 个月（95%CI 0.7-46.8 个月）。单因素分析显示，世界卫生组织（WHO）体能状态≥1、存在骨、肝和胸膜腹膜转移与较差的 PFS 和 OS 相关。多因素分析表明，只有胸膜腹膜转移与 PFS 和 OS 独立相关。存在胸膜腹膜转移和 WHO 体能状态≥1 的患者从 CKI 中获益的可能性<10%。
我们的数据支持胸膜腹膜转移是影响 NSCLC 患者 CKI 疗效的主要预测因素的假设，并且可以用于避免此类患者的 CKI 单药治疗。
