Department of Thoracic Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands.
Cancer. 2024 Mar 1;130(5):683-691. doi: 10.1002/cncr.35090. Epub 2023 Oct 31.
Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutations in patients with non-small cell lung cancer (NSCLC) and are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). There is evidence of activity of combining EGFR TKIs with monoclonal antibodies. This study reports on the efficacy and safety of afatinib in combination with cetuximab.
In this single-arm phase 2 trial, patients with advanced NSCLC harboring an EGFR ex20ins mutation were treated with afatinib 40 mg once daily in combination with cetuximab 500 mg/m every 2 weeks. The primary end point was disease control rate (DCR) at 18 weeks of treatment.
Thirty-seven patients started treatment, with a median age of 65 years (range, 40-80 years), 78% female, and 95% White. The study achieved its primary end point with a DCR of 54% at 18 weeks, an overall response rate (ORR) of 43%, and a 32% confirmed ORR. Best responses were partial (n = 16), stable (n = 16), progressive disease (n = 2), or not evaluable (n = 3). Median progression-free survival was 5.5 months (95% CI, 3.7-8.3 months) and median overall survival was 16.8 months (95% CI, 10.7-25.8 months). The most common treatment-related adverse events (TRAEs) were diarrhea (70%), rash (65%), dry skin (59%), paronychia (54%), and erythema (43%). Grade 3 TRAEs were reported in 54% of all patients.
Combination treatment with afatinib and cetuximab demonstrated antitumor activity with a DCR of 54% at 18 weeks and a 32% confirmed ORR. Toxicity was significant, although manageable, after dose reduction.
表皮生长因子受体（EGFR）外显子 20 插入（ex20ins）突变是非小细胞肺癌（NSCLC）患者中第三常见的 EGFR 突变，与 EGFR 酪氨酸激酶抑制剂（TKI）的原发性耐药相关。有证据表明，将 EGFR TKI 与单克隆抗体联合使用具有活性。本研究报告了阿法替尼联合西妥昔单抗的疗效和安全性。
在这项单臂 2 期试验中，患有 EGFR ex20ins 突变的晚期 NSCLC 患者接受每日一次 40mg 阿法替尼联合每 2 周一次 500mg/m 的西妥昔单抗治疗。主要终点是治疗 18 周时的疾病控制率（DCR）。
37 例患者开始治疗，中位年龄为 65 岁（范围，40-80 岁），78%为女性，95%为白人。该研究达到了主要终点，18 周时 DCR 为 54%，总缓解率（ORR）为 43%，确认的 ORR 为 32%。最佳反应为部分缓解（n=16）、稳定（n=16）、进展性疾病（n=2）或无法评估（n=3）。中位无进展生存期为 5.5 个月（95%CI，3.7-8.3 个月），中位总生存期为 16.8 个月（95%CI，10.7-25.8 个月）。最常见的治疗相关不良事件（TRAEs）是腹泻（70%）、皮疹（65%）、皮肤干燥（59%）、甲沟炎（54%）和红斑（43%）。所有患者中有 54%发生 3 级 TRAEs。
阿法替尼联合西妥昔单抗治疗显示出抗肿瘤活性，18 周时 DCR 为 54%，确认的 ORR 为 32%。毒性虽然可管理，但在剂量减少后仍很明显。
