The efficacy and safety of adding anlotinib in gradual progression on third-generation EGFR-TKIs for EGFR-mutant advanced non-small cell lung cancer

Background: Acquired resistance is unavoidable with the approval of third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for first-line therapy of advanced non-small cell lung cancer (NSCLC). Some studies have found that combining anti-angiogenesis medicines with EGFR-TKI may benefit clinical outcomes in EGFR-mutant NSCLC. However, it is unclear whether EGFR TKI paired with anti-angiogenesis therapy could further improve survival for patients with gradual progression. Thus, we evaluated the clinical effectiveness and safety of continuous EGFR-TKI in combination with anlotinib in patients who had gradual progression on third-generation EGFR-TKI treatment. Methods: The effectiveness and safety of anlotinib coupled with continuous EGFR-TKI versus EGFR-TKI monotherapy in EGFR-mutant patients treated with first-line third-generation EGFR-TKIs in gradual progression were compared. The efficacy and safety were analyzed. The compare of progression-free survival (PFS) and overall survival (OS) between two groups was used the Kaplan-Meier method. Results: Our study comprised 121 eligible patients in total.In the combination group, there were 60 patients, while in the EGFR-TKI monotherapy group, there were 61 patients. The objectiveresponse rates (ORR) were 25.0% and 0%, the disease response rate (DCR) was 91.7% and 86.9% in combination group and EGFR-TKIs monotherapy group. The median PFS of combinedanlotinib and EGFR-TKIs treatment were 6.7 months and mPFS was 3.6 months in the EGFR-TKI monotherapy group (P <0.001). Regarding the OS, there were no significant differences between the two groups. The common adverse reaction were diarrhea(21.7%), hypertension (21.6%) and proteinuria (20.0%) in combination group. Seven patients experienced the grade 3 or higher adverse event, no patients discounted the treatment or died due to the toxicity. Conclusion: The results of our study indicated that, when combined with anlotinib following gradual progression on EGFR-TKIs, it was more efficacious for EGFR mutant NSCLC patients than EGFR TKI monotherapy. And the toxicity was clinically manageable.