Low-dose anlotinib confers improved survival in combination with immune checkpoint inhibitor in advanced non-small cell lung cancer patients

Cancer Immunol Immunother. 2023 Feb;72(2):437-448. doi: 10.1007/s00262-022-03259-5. Epub 2022 Aug 5.

Abstract

Background: Anti-angiogenic drugs increase anti-tumor efficacy of immune checkpoint inhibitors (ICIs). However, the optimal dose of anti-angiogenic drugs remains unclear.

Methods: We retrospectively analyzed efficacy and safety data from patients diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) that received PD-1 blockade with low-doses of anlotinib, a highly selective receptor tyrosine kinase inhibitor mainly targeting vascular endothelial growth factor receptors, as second or later line therapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety profile. Univariate and multivariate analyses were used to identify prognostic factors.

Results: A total of 40 eligible patients were included. The median PFS was 11.4 months. The median OS of the entire cohort was 27.0 months. ORR was achieved in 16 patients (40.0%) and DCR was maintained in 33 patients (82.5%). The overall incidence of adverse events (AEs) was 52.5%, and the most common all grade AE was gastrointestinal reactions, which occurred in four patients (10.0%). Treatment-related grade 3/4 toxicity was observed in one patient (2.5%). Conclusions Low-dose anlotinib may be an effective and well-tolerated anti-angiogenesis partner for combination therapy with ICIs in second-line and later settings for advanced NSCLC.

Keywords: Anti-angiogenic drugs; Combination therapy; ICIs; NSCLC; Second-line treatment.

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Indoles / therapeutic use
  • Lung Neoplasms* / drug therapy
  • Quinolines* / therapeutic use
  • Retrospective Studies

Substances

  • Angiogenesis Inhibitors
  • anlotinib
  • Immune Checkpoint Inhibitors
  • Quinolines
  • Indoles