A retrospective study of anlotinib plus third-generation EGFR-TKIs in advanced non-small cell lung cancer with gradual or oligo progression after EGFR-TKIs treatment (ALTER-L058).

Abstract

8600 Background: Despite the significant improvement in progression-free survival (PFS) for non-small cell lung cancer (NSCLC) patients with EGFR mutations, attributed to the advent of third-generation EGFR tyrosine kinase inhibitors (TKIs), the inevitable development of acquired resistance continues to pose a critical challenge that severely affects the long-term efficacy of these treatments. This study aims to evaluate the efficacy and safety of anlotinib in combination with third-generation EGFR-TKIs in advanced NSCLC patients experiencing gradual or oligo progression following EGFR-TKIs. Methods: ALTER-L058 was a retrospective study conducted at 16 hospitals in China. Eligible patients aged 18 to 75 years with histologically or cytologically confirmed NSCLC who tested positive for EGFR mutations and exhibited gradual or oligo progression following treatment with third-generation EGFR-TKIs. Patients continued their regimen of EGFR-TKIs with or without anlotinib after gradual or oligo progression. Anlotinib was administered orally at a dose of 8-12 mg per day for two weeks, followed by a one-week break, within a three-week cycle. The primary endpoint was PFS. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. Results: From 1/2020 to 12/2023, a total of 150 patients were enrolled in the study. Among these, 100 patients received third-generation EGFR-TKIs plus anlotinib treatment, while 50 patients only received third-generation EGFR-TKIs. From treatment initiation of EGFR-TKIs, compared with third-generation EGFR-TKIs alone, median PFS was prolonged with third-generation EGFR-TKIs plus anlotinib (23.2 versus 19.5 months; hazard ratio (95%CI): 0.56 (0.36-0.86); P = 0.0008). From gradual or oligo progression after EGFR-TKIs treatment, mPFS was significantly extended with the combination of third-generation EGFR TKIs and anlotinib compared to third-generation EGFR TKIs alone (9.2 versus 5.4 months; hazard ratio (95%CI): 0.40 (0.25-0.65); P＜0.0001). The incidence of grade 3 or higher treatment-related adverse events was 37.0% (third-generation EGFR-TKIs plus anlotinib) and 34.0% (third-generation EGFR-TKIs), respectively. Conclusions: Continuous treatment with anlotinib after the emergence of gradual or oligo progression during the third-generation EGFR-TKIs therapy prolonged the clinical benefit of EGFR-TKIs, demonstrating favorable survival outcomes and manageable toxicity. Clinical trial information: ChiCTR2500095741 .