Efficacy and safety of anlotinib in bevacizumab-pretreated patients with non-squamous non-small cell lung cancer (AN-BELIEF study): a multicenter retrospective study

Background: Given the growing population of patients with disease progression following bevacizumab-based regimens, effective post-bevacizumab antiangiogenic options remain an unmet need. We aimed to evaluate the efficacy and safety of anlotinib in this specific population of non-squamous non-small cell lung cancer (NSCLC).

Methods: This multicenter retrospective cohort study enrolled patients from six hospitals between January 2018 and May 2024. Eligible patients had non-squamous NSCLC and received bevacizumab-containing treatment, or received anlotinib monotherapy without prior bevacizumab exposure. Key exclusions included anlotinib initiation before bevacizumab treatment, the use of other antiangiogenic tyrosine kinase inhibitors after bevacizumab, or insufficient radiologic evaluation. Patients were grouped by prior bevacizumab exposure and subsequent treatment. Tumor response was assessed by investigators according to response evaluation criteria in solid tumors (RECIST) version 1.1, with progression-free survival (PFS) as the primary endpoint; secondary endpoints included the objective response rate (ORR) and disease control rate (DCR), and adverse events (AEs), with AEs assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Results: Of 1,256 screened patients, 746 were included in the original cohort: 174 bevacizumab-naïve (bevacizumab-naïve) patients who received anlotinib monotherapy, and 572 bevacizumab-pretreated patients who were further divided into anlotinib monotherapy (n=108), anlotinib-based combination therapy (n=345), or other therapies (n=119). In the cohort, bevacizumab-naïve patients attained significantly longer PFS than bevacizumab-pretreated patients receiving anlotinib monotherapy [8.23 vs. 5.90 months; hazard ratio (HR), 1.41; P=0.003]. However, after propensity score matching (PSM) to balance covariates, this difference was no longer significant (6.43 vs. 7.60 months; HR 1.14, P=0.33). Among bevacizumab-pretreated patients, PFS did not differ significantly among the three treatment groups before matching (P=0.42); after PSM, anlotinib monotherapy and other therapies showed similar PFS (5.90 vs. 5.23 months; HR 0.96, P=0.77), whereas anlotinib combination therapy group was associated with a significantly longer PFS compared with other therapies (6.50 vs. 5.23 months; HR 0.82, P=0.048).

Conclusions: Anlotinib showed clinical activity in this selected retrospective cohort of bevacizumab-pretreated patients with non-squamous NSCLC. Anlotinib-based combination therapy was associated with longer PFS than other subsequent therapies after adjustment for baseline differences; however, these findings require confirmation in larger prospective studies.