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

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.