Survival benefit of anlotinib in T790M‐positive non‐small‐cell lung cancer patients with acquired osimertinib resistance: A multicenter retrospective study and exploratory in vitro study

Abstract

Abstract Objectives Acquired resistance represents a bottleneck to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in lung cancer. Our study aimed to explore the efficacy of antiangiogenic‐based therapy in osimertinib‐resistant NSCLC patients and assess the efficacy of anlotinib in vitro study. Methods Our multicenter study retrospectively collected 268 osimertinib‐resistant NSCLC patients with EGFR T790M mutation and explored the efficacy of anlotinib in patients and in vitro. Results PFS was significantly longer in the antiangiogenic‐based therapy group than in the immunotherapy group (HR: 0.71, p = 0.050) and the chemotherapy group (HR: 0.28, p = 0.001). Both the ORR and DCR of the antiangiogenic‐based group were higher than the immunotherapy group and the chemotherapy group. Subgroup analysis showed a trend of more benefits from the anlotinib‐based therapy than the bevacizumab‐based therapy in terms of PFS (HR: 0.63, p = 0.087) and OS (HR: 0.52, p = 0.063). In vitro assays verified that anlotinib alone or combined with osimertinib exerted potent cytotoxicity to T790M‐mutant H1975 cell line with acquired osimertinib resistance. Conclusions Our study suggested that antiangiogenic‐based therapy might improve PFS and OS in EGFR‐mutant NSCLC patients with acquired resistance to osimertinib. Moreover, anlotinib‐based therapy could be a promising effective treatment for this group of patients.

Keywords

• anlotinib
• non‐small‐cell lung cancer
• osimertinib
• resistance