anlotinib + gefitinib

The combination of anlotinib and gefitinib is a dual-targeting therapeutic approach for non-small cell lung cancer (NSCLC), particularly for patients with EGFR mutations. This combination has been studied in various clinical settings, including as first-line treatment for untreated EGFR-mutant NSCLC and for patients who have developed resistance to EGFR-TKIs. ## Mechanism of Action Anlotinib is a multi-targeted tyrosine kinase inhibitor that effectively inhibits VEGFRs, FGFRs, PDGFRs, c-kit, and MET, primarily functioning as an anti-angiogenic agent. Gefitinib is an EGFR tyrosine kinase inhibitor (EGFR-TKI) that targets the EGFR pathway, which is commonly mutated in certain types of NSCLC[1][2]. The combination works through dual blockade of the EGFR and VEGF pathways, which has been demonstrated to be a viable strategy in EGFR-mutated advanced NSCLC. Preclinical studies have shown that this combination significantly inhibits the proliferation of EGFR-TKI-resistant NSCLC cells in vitro and tumor angiogenesis in vivo[1][3]. ## Clinical Evidence Several clinical studies have evaluated this combination: - A study from April 2018 to June 2020 enrolled 20 patients with advanced NSCLC who had developed potential acquired drug resistance after receiving gefitinib or icotinib. Adding anlotinib to the original targeted drug showed promising results[1]. - An exploratory clinical study reported that gefitinib combined with anlotinib for patients with first-line non-small cell lung cancer who progressed slowly showed a median progression-free survival of 13.3 months, with manageable adverse events[4]. - A phase III study was designed to evaluate the efficacy and safety of anlotinib or placebo plus gefitinib in patients with untreated EGFR-mutated metastatic NSCLC[2][5]. ## Safety Profile The combination therapy has shown a generally favorable safety profile. Common adverse reactions reported include hypertension, hand-foot-skin reaction, diarrhea, fatigue, oral ulcers, and anorexia, but most were mild (Grade 1)[3][4]. In one study, no higher-grade adverse reactions were reported, suggesting the combination is well-tolerated[4]. ## Development Status This combination is being actively investigated in clinical trials, including a multicenter, randomized, double-blind phase III study for untreated EGFR-mutated metastatic NSCLC[2][5]. The promising results from early studies suggest it could become an important treatment option, particularly for patients with EGFR-TKI resistance.