Background

Nivolumab is the first checkpoint inhibitor approved for the treatment of nonsquamous non–small-cell lung cancer (nonsq–NSCLC). We report results from the nivolumab Italian expanded access program (EAP), focusing on never-smokers and EGFR-mutant patients with nonsq–NSCLC.

Patients and Methods

Nivolumab (3 mg/kg intravenously every 2 weeks) was administered upon physicians’ request for patients who had relapsed after ≥1 prior systemic treatment for stage IIIB/IV nonsq–NSCLC. Efficacy and safety were evaluated in patients who received ≥1 nivolumab dose.

Results

Of 1,588 patients with nonsq–NSCLC, 305 (19.2%) were never-smokers. EGFR status was available for 1,395 patients. Of 102 (6.4%) patients with EGFR-mutation–positive tumors, 51 (50%) were never-smokers. Objective response rate (ORR) was significantly higher in EGFR wild-type than EGFR-mutant patients (19.6% vs 8.8%; P=0.007), in former/current smokers than never-smokers (21.5% vs 9.2%; P=0.0001), and in EGFR wild-type than EGFR-mutant never-smokers (11.0% vs 1.9%; P=0.04). There was no significant difference in ORR between EGFR wild-type and EGFR-mutant smokers (22.0% vs 20.6%). There was no statistically significant difference in median progression-free survival (PFS) and in median overall survival (OS). Specifically median OS was 11.0 vs 8.3 months in patients with EGFR wild-type vs EGFR-mutant tumors, 11.6 vs 10.0 months in smokers vs never-smokers, 11.0 vs 5.6 months in never-smokers with EGFR wild-type vs mutant tumors, and 14.1 vs 11.3 months in smokers with EGFR-mutant vs wild-type tumors.

Conclusions

Italian EAP data in nonsq–NSCLC populations suggest that subgroups of patients could benefit differently from nivolumab according to EGFR mutational status and smoking habits. These results warrant further investigation.

中文翻译：

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意大利nivolumab扩大了针对非鳞状非小细胞肺癌患者的治疗方案：导致从不吸烟者和EGFR突变患者

背景

Nivolumab是首个被批准用于治疗非鳞状非小细胞肺癌（nonsq-NSCLC）的检查点抑制剂。我们报告了来自nivolumab意大利扩展访问计划（EAP）的结果，重点关注了非吸烟者和EGFR突变的非sq-NSCLC患者。

患者和方法

根据医师的要求，对于IIIB / IV期非sq-NSCLC≥1次全身性治疗后复发的患者，应医生要求使用Nivolumab（每2周静脉注射3 mg / kg）。接受≥1 nivolumab剂量的患者的疗效和安全性进行了评估。

结果

在1,588名非sq–NSCLC患者中，有305名（19.2％）从不吸烟。1,395名患者的EGFR状态可用。在102位（6.4％）EGFR突变阳性肿瘤患者中，有51位（50％）从未吸烟。EGFR野生型患者的客观缓解率（ORR）显着高于EGFR突变患者（19.6％vs.8.8％; P = 0.007），既往/现吸烟者比不吸烟者（21.5％vs 9.2％; P = 0.0001） ），并且在EGFR野生型中比EGFR突变型永不吸烟者（11.0％对1.9％；P = 0.04）。EGFR野生型和EGFR之间的ORR无显着差异-突变吸烟者（22.0％比20.6％）。中位数无进展生存期（PFS）和中位数总体生存期（OS）没有统计学上的显着差异。EGFR野生型与EGFR突变肿瘤患者的OS中位数分别为11.0 vs 8.3个月，吸烟者与从不吸烟者的吸烟者中位OS为11.6 vs 10.0个月，EGFR野生型与突变的患者的不吸烟者中位OS为11.0 vs 5.6个月，以及EGFR突变型患者与野生型肿瘤吸烟者分别为14.1个月和11.3个月。

结论

非sq-NSCLC人群中的意大利EAP数据表明，根据EGFR突变状态和吸烟习惯，患者亚组可从nivolumab中获益不同。这些结果值得进一步调查。