Univ. Lille, CHU Lille, Thoracic Oncology Department, CNRS, Inserm, Institut Pasteur de Lille, UMR9020, UMR-S 1277, Canther, Lille, France.
Intergroupe Francophone de Cancérologie Thoracique (IFCT), Paris, France.
Clin Cancer Res. 2021 Aug 1;27(15):4168-4176. doi: 10.1158/1078-0432.CCR-20-4604. Epub 2021 May 24.
Double inhibition of epidermal growth factor receptor (EGFR) using a tyrosine kinase inhibitor plus a monoclonal antibody may be a novel treatment strategy for non-small cell lung cancer (NSCLC). We assessed the efficacy and toxicity of afatinib + cetuximab versus afatinib alone in the first-line treatment of advanced -mutant NSCLC.
In this phase II, randomized, open-label study, patients with stage III/IV -positive NSCLC were randomly assigned (1:1) to receive afatinib (group A) or afatinib + cetuximab (group A + C). Oral afatinib 40 mg was given once daily; cetuximab 250 mg/m² was administered intravenously on day 15 of cycle 1, then every 2 weeks at 500 mg/m² for 6 months. The primary endpoint was time to treatment failure (TTF) rate at 9 months. Exploratory analysis of circulating tumor DNA in plasma was performed.
Between June 2016 and November 2018, 59 patients were included in group A and 58 in group A + C. The study was ended early after a futility analysis was performed. The percentage of patients without treatment failure at 9 months was similar for both groups (59.3% for group A vs. 64.9% for group A + C), and median TTF was 11.1 (95% CI, 8.5-14.1) and 12.9 (9.2-14.5) months, respectively. Other endpoints, including progression-free survival and overall survival, also showed no improvement with the combination versus afatinib alone. There was a slight numerical increase in grade ≥3 adverse events in group A + C. Allele frequency of the gene mutation in circulating tumor DNA at baseline was associated with shorter PFS, regardless of the treatment received.
These results suggest that addition of cetuximab to afatinib does not warrant further investigation in treatment-naïve advanced -mutant NSCLC.
表皮生长因子受体（EGFR）的双重抑制作用，即使用酪氨酸激酶抑制剂联合单克隆抗体，可能是治疗非小细胞肺癌（NSCLC）的一种新策略。我们评估了 afatinib + cetuximab 对比 afatinib 单药一线治疗晚期 EGFR 突变 NSCLC 的疗效和毒性。
这是一项 II 期、随机、开放标签研究，纳入 III/IV 期 EGFR 阳性 NSCLC 患者，按 1:1 随机分组（A 组接受 afatinib，A + C 组接受 afatinib + cetuximab）。A 组患者口服 afatinib 40 mg，每日 1 次；A + C 组患者第 1 周期第 15 天静脉输注 cetuximab 250 mg/m²，之后每 2 周 500 mg/m²，持续 6 个月。主要终点为 9 个月时的治疗失败时间（TTF）率。对血浆循环肿瘤 DNA 进行了探索性分析。
2016 年 6 月至 2018 年 11 月，共纳入 59 例 A 组患者和 58 例 A + C 组患者。经过无效性分析后，该研究提前结束。两组患者在 9 个月时无治疗失败的比例相似（A 组 59.3%，A + C 组 64.9%），中位 TTF 分别为 11.1（95%CI，8.5-14.1）和 12.9（9.2-14.5）个月。其他终点，包括无进展生存期和总生存期，联合治疗与 afatinib 单药治疗相比也没有改善。A + C 组患者的 3 级及以上不良事件发生率略有增加。无论接受何种治疗，基线时基因 突变的循环肿瘤 DNA 等位基因频率与较短的 PFS 相关。
这些结果表明，在初治晚期 EGFR 突变 NSCLC 患者中，cetuximab 联合 afatinib 治疗不应进一步研究。
