Introduction: Anti‐EGFR agents are standard treatments for patients with EGFR‐mutant advanced NSCLC. The feasibility of combining erlotinib or gefitinib with the anti–programmed death 1 immunotherapy pembrolizumab was evaluated in the phase 1/2 KEYNOTE‐021 study (NCT02039674). Methods: Adults with previously untreated stage IIIB/IV EGFR‐mutant NSCLC were treated with pembrolizumab 2 mg/kg intravenously every 3 weeks plus oral erlotinib 150 mg daily in cohort E or oral gefitinib 250 mg daily in cohort F, using a 3 + 3 design with cohort expansion. rTumor response was evaluated per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review. The primary objective was determination of a recommended phase 2 dose. Results: Twelve patients enrolled to receive pembrolizumab plus erlotinib and seven to receive pembrolizumab plus gefitinib. No dose‐limiting toxicities or grade 5 events occurred. Pembrolizumab plus erlotinib was feasible, with adverse events similar to those expected for monotherapy. However, pembrolizumab plus gefitinib was not feasible due to grade 3/4 liver toxicity in five of seven patients (71.4%), leading to permanent treatment discontinuation in four patients. The most frequently occurring treatment‐related adverse events with pembrolizumab plus erlotinib were rash (50.0%), dermatitis acneiform, diarrhea, hypothyroidism, and pruritus (33.3% each). The objective response rate was 41.7%, including response in all four patients with programmed death ligand 1 expression 50% or greater. Conclusions: Although pembrolizumab plus gefitinib was not feasible, the toxicity profile observed with pembrolizumab plus erlotinib suggests combining immunotherapy with anti‐EGFR therapy is feasible. Pembrolizumab plus erlotinib did not improve objective response rate compared with previous monotherapy studies; further evaluation would be necessary to evaluate potential effects on other efficacy outcomes.

中文翻译：

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简报：派姆单抗联合厄洛替尼或吉非替尼作为晚期非小细胞肺癌敏感 EGFR 突变的一线治疗

简介：抗 EGFR 药物是 EGFR 突变的晚期 NSCLC 患者的标准治疗方法。1/2 期 KEYNOTE-021 研究 (NCT02039674) 评估了厄洛替尼或吉非替尼与抗程序性死亡 1 免疫疗法派姆单抗联合的可行性。方法：先前未治疗的 IIIB/IV 期 EGFR 突变 NSCLC 成人每 3 周静脉注射帕博利珠单抗 2 mg/kg，并在队列 E 中每天口服厄洛替尼 150 mg 或在队列 F 中每天口服吉非替尼 250 mg，使用 3 + 3设计与队列扩展。rTumor 反应根据实体瘤 1.1 版中的反应评估标准通过盲法独立中央审查进行评估。主要目标是确定推荐的 2 期剂量。结果：12 名患者入组接受 pembrolizumab 加厄洛替尼治疗，7 名患者接受 pembrolizumab 加吉非替尼治疗。没有发生剂量限制性毒性或 5 级事件。派姆单抗加厄洛替尼是可行的，其不良事件与单药治疗的预期相似。然而，由于 7 名患者中有 5 名 (71.4%) 出现 3/4 级肝毒性，派姆单抗加吉非替尼不可行，导致 4 名患者永久停止治疗。帕博利珠单抗加厄洛替尼最常发生的治疗相关不良事件是皮疹 (50.0%)、痤疮样皮炎、腹泻、甲状腺功能减退和瘙痒 (各 33.3%)。客观反应率为 41.7%，包括所有四名程序性死亡配体 1 表达 50% 或更高的患者的反应。结论：尽管帕博利珠单抗加吉非替尼不可行，但帕博利珠单抗加厄洛替尼观察到的毒性特征表明将免疫疗法与抗 EGFR 疗法相结合是可行的。与之前的单药治疗研究相比，派姆单抗加厄洛替尼并未提高客观缓解率；需要进一步评估以评估对其他功效结果的潜在影响。