Anlotinib added to third generation EGFR tyrosine kinase inhibitor therapy for advanced NSCLC patients with oligo-progression: a retrospective study (ALTER-L058).

Objective: To investigate the efficacy of anlotinib, an antiangiogenic multikinase inhibitor, as an add-on therapy to first-line epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) for patients with EGFR-mutant non-small cell lung cancer (NSCLC) who were previously untreated before first-line EGFR TKI but subsequently developed oligoprogression. Methods: This multicenter, retrospective cohort study (ALTER-L058) analyzed data from the electronic health records-derived de-identified systems at 16 cancer centers in China. Adult patients between 18 and 75 years of age with histologically or cytologically confirmed locally advanced or metastatic NSCLC who received first-line third-generation EGFR TKI monotherapy and had an oligoprogressive disease were included. Eligible patients received anlotinib (8, 10 or 12 mg) on days 1-14 of each 3-week cycle for ≥6 cycles. Tumor response was assessed radiologically by investigators per RECIST, version 1.1. The primary outcome was investigators-assessed progression-free survival, calculated from the date of medication initiation for the oligoprogressive disease to the first documented progressive disease or death. Results: Between January 2020 and December 2023, 100 patients received EGFR TKI plus anlotinib and 50 received EGFR TKI. At the data cutoff (20 November 2024), the median progression-free survival was 9.23 months (95% CI, 8.94-10.87) with EGFR TKI plus anlotinib versus 5.42 months (95% CI, 4.83-6.80) with EGFR TKI (hazard ratio [HR] = 0.38, 95% CI, 0.26-0.56; log rank test, P < 0.0001), meeting the primary endpoint. Anlotinib was generally well tolerated, with manageable adverse events. Conclusion: Anlotinib, when added onto EGFR TKI therapy following gradual progression or oligo-progression, conferred significant PFS benefits upon EGFR mutant NSCLC patients, supporting adding anlotinib to ongoing first-line EGFR TKI therapy for oligoprogressive disease.