Abstract
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.