Shi Huiyang, Wang Miaohan, Li Junling, Jin Shi, Zhuo Minglei, Zhao Jun, Zhang Hongxia, Yang Meng, Shi Qingfang, Qin Haifeng, Dong Guilan, Lan Dongmei, Dai Zhong, Feng Yu, Zhu Haohua, Lu Jingyu, Zhu Kai, Shi Yuankai, Hu Xingsheng
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.
Thorac Cancer. 2025 Aug;16(15):e70137. doi: 10.1111/1759-7714.70137.
BACKGROUND: Studies indicated that afatinib combined with angiogenesis inhibitor may achieve promising efficacy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. METHODS: This is a multicenter, Phase II trial to explore the efficacy and safety of afatinib plus bevacizumab at first-line setting for EGFR-mutant NSCLC patients. The primary end point was progression-free survival (PFS). The secondary end point included objective response rate (ORR), disease control rate (DCR) and safety. RESULTS: Between July 11, 2020 and November 11, 2021, 54 treatment-naïve NSCLC patients were enrolled in the afatinib plus bevacizumab combination cohort. Meanwhile, 81 NSCLC patients with EGFR mutations treated with first-line afatinib monotherapy were retrospectively collected. The median follow-up time was 26.6 months. No significant difference in PFS was observed between the afatinib plus bevacizumab combination cohort and the afatinib monotherapy cohort (14.5 vs. 12.2 months, HR 0.87, p = 0.15), confirmed by propensity score matching (PSM) analysis. Patients with pleural metastasis (HR 0.56, 95% CI: 0.32-0.98, p < 0.05) and uncommon EGFR mutations (HR 0.61, 95% CI: 0.25-1.47, p = 0.05) experienced longer PFS in the combination cohort. ORR in the combination cohort is more favorable than in the afatinib monotherapy cohort (77.8% vs. 42.0%, p < 0.05). Diarrhea was the most common treatment-related adverse events (TRAEs). 11.1% (6/54) patients had grade ≥ 3 TRAEs when treated with afatinib plus bevacizumab. CONCLUSION: Afatinib combined with bevacizumab is well tolerated with moderate efficacy among patients with NSCLC, which might be a prospective strategy for patients with uncommon EGFR mutations and pleural metastasis. TRIAL REGISTRATION: www.chictr.org.cn.
背景：研究表明，阿法替尼联合血管生成抑制剂在表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者中可能取得有前景的疗效。 方法：这是一项多中心II期试验，旨在探索阿法替尼联合贝伐单抗一线治疗EGFR突变NSCLC患者的疗效和安全性。主要终点是无进展生存期（PFS）。次要终点包括客观缓解率（ORR）、疾病控制率（DCR）和安全性。 结果：在2020年7月11日至2021年11月11日期间，54例初治NSCLC患者入组阿法替尼联合贝伐单抗治疗组。同时，回顾性收集81例接受一线阿法替尼单药治疗的EGFR突变NSCLC患者。中位随访时间为26.6个月。倾向评分匹配（PSM）分析证实，阿法替尼联合贝伐单抗治疗组与阿法替尼单药治疗组的PFS无显著差异（14.5个月对12.2个月，HR 0.87，p = 0.15）。有胸膜转移的患者（HR 0.56，95%CI：0.32 - 0.98，p < 0.05）和罕见EGFR突变的患者（HR 0.61，95%CI：0.25 - 1.47，p = 0.05）在联合治疗组中PFS更长。联合治疗组的ORR优于阿法替尼单药治疗组（77.8%对42.0%，p < 0.05）。腹泻是最常见的治疗相关不良事件（TRAEs）。11.1%（6/54）的患者在接受阿法替尼联合贝伐单抗治疗时发生≥3级TRAEs。 结论：阿法替尼联合贝伐单抗在NSCLC患者中耐受性良好，疗效中等，这可能是罕见EGFR突变和胸膜转移患者的一种前瞻性策略。 试验注册：www.chictr.org.cn。
Cochrane Database Syst Rev. 2016-5-25
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