Introduction: This phase I study evaluated nivolumab combined with erlotinib in patients with advanced EGFR‐mutant NSCLC. Methods: Patients with advanced EGFR‐mutant NSCLC who were EGFR tyrosine kinase inhibitor (TKI)–naive or TKI‐treated but had not received chemotherapy were treated with nivolumab 3 mg/kg every 2 weeks and erlotinib 150 mg/d until disease progression or unacceptable toxicity. The primary objective was safety and tolerability. Results: Twenty patients with TKI‐treated and one with TKI‐naive EGFR‐mutant NSCLC were treated with nivolumab plus erlotinib. Treatment‐related grade 3 toxicities occurred in five patients (liver enzyme elevations, n = 2; diarrhea, n = 2; weight loss, n = 1), with no grade ≥4 toxicities. In the TKI‐treated population, the objective response rate was 15% (3 of 20, including one complete response), and the 24‐week progression‐free survival rate was 48%. Responses lasted 13.8, 17.6, and 38.2 months per investigator records. A fourth patient had a nonconventional immune‐related response lasting 12.5 months. Among these four patients, two were never‐smokers and one each had 35– and <1‐pack‐year histories. Post‐EGFR TKI pre‐trial tumor biopsy specimens from these patients detected EGFR T790M mutations in two patients and MNNG HOS Transforming gene (MET) amplification in a third; two patients each had primary EGFR exon 19 deletions or L858R mutations. The TKI‐naive patient, who had compound EGFR mutations (L858R and S768I) and ultimately achieved a complete response, had an ongoing response lasting more than 5 years based on investigator records. Conclusions: Nivolumab plus erlotinib was tolerable, with durable responses in patients with EGFR‐mutant, TKI‐treated NSCLC.

中文翻译：

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纳武单抗加厄洛替尼治疗表皮生长因子受体突变晚期非鳞状非小细胞肺癌患者

简介：这项 I 期研究在晚期 EGFR 突变 NSCLC 患者中评估了纳武单抗联合厄洛替尼。方法： EGFR 酪氨酸激酶抑制剂（TKI）初治或 TKI 治疗但未接受化疗的晚期 EGFR 突变 NSCLC 患者每 2 周接受 nivolumab 3 mg/kg 和厄洛替尼 150 mg/d 治疗，直至疾病进展或不可接受的毒性。主要目标是安全性和耐受性。结果：20 名接受过 TKI 治疗的患者和 1 名接受过 TKI 治疗的 EGFR 突变 NSCLC 患者接受了纳武单抗加厄洛替尼治疗。5 名患者出现治疗相关的 3 级毒性（肝酶升高，n = 2；腹泻，n = 2；体重减轻，n = 1），没有≥4 级毒性。在接受 TKI 治疗的人群中，客观反应率为 15%（20 人中有 3 人，包括 1 人完全反应），24 周无进展生存率为 48%。每个研究者记录的反应持续了 13.8、17.6 和 38.2 个月。第四名患者的非常规免疫相关反应持续了 12.5 个月。在这四名患者中，两名从不吸烟，一名有 35 年和 <1 包年的病史。来自这些患者的 EGFR TKI 试验前肿瘤活检标本在两名患者中检测到 EGFR T790M 突变，在第三名患者中检测到 MNNG HOS 转化基因（MET）扩增；两名患者各有原发性 EGFR 外显子 19 缺失或 L858R 突变。根据研究者记录，TKI 初治患者具有复合 EGFR 突变（L858R 和 S768I）并最终获得完全缓解，持续缓解持续超过 5 年。结论：纳武单抗加厄洛替尼是可以耐受的，