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Multicenter Study
. 2023 Aug;12(15):15922-15932.
doi: 10.1002/cam4.6232. Epub 2023 Jun 30.

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

Ya Chen  1 , Hongyu Liu  2 , Nana Hu  1 , Yanan Wang  3 , Zhengyu Yang  4 , Junqiang Zhang  1 , Baohui Han  2
Affiliations
Multicenter Study

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

Ya Chen et al. Cancer Med. 2023 Aug.

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.

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Conflict of interest statement

The authors declares no conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) Progression‐free survival and (B) overall survival of patients with acquired osimertinib resistance NSCLC in the overall population. 95% confidence intervals are shown in light colors.
FIGURE 2
FIGURE 2
Kaplan–Meier analysis of (A) progression‐free survival and (B) overall survival of patients with acquired osimertinib resistance NSCLC treated with antiangiogenic‐based therapy (Angio), immunotherapy (Immuno) or chemotherapy (Chemo).
FIGURE 3
FIGURE 3
The ORR and DCR of patients in the antiangiogenic‐based therapy group (Angio), immunotherapy group (Immuno) and chemotherapy group (Chemo).
FIGURE 4
FIGURE 4
Kaplan–Meier analysis of progression‐free survival and overall survival of antiangiogenic therapy subgroups: (A) PFS before PS matching, (B) PFS after PS matching, (C) OS before PS matching and (D) OS after PS matching.
FIGURE 5
FIGURE 5
Cell viability assay of H1975OR cell line treated with osimertinib or anlotinib for 3 days(A, B). Cell viability assay of H1975OR and H1975 cell line treated with anlotinib and/or osimertinib at indicated concentrations for 3 days (C, D). Cell growth and viability of H1975OR cell line treated with anlotinib and/or osimertinib at indicated concentrations for 3 days (E, F). Colony formation assay of H1975OR cell line treated with anlotinib and/or osimertinib for 7 days (G, H). **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001.
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