Osimertinib plus anlotinib in untreated, EGFR-mutated, advanced non-small-cell lung cancer with concurrent alterations: a multicenter phase II study

Vollständiger Abstract

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Abstract Background The standard first-line treatment for advanced EGFR-mutated non-small cell lung cancer (NSCLC) is EGFR tyrosine kinase inhibitors. However, concurrent mutations facilitate resistance evolution in EGFR-mutant lung adenocarcinoma and combination therapies may offer a superior approach. This study explores the efficacy and safety of osimertinib plus anlotinib as first-line treatment for advanced NSCLC with EGFR co-mutations. Materials and Methods This study prospectively enrolled patients with advanced NSCLC harboring EGFR (19Del/21L858R) mutations and ≥1 mutation in TP53, PIK3CA, or RB1, who had not undergone systemic treatment. Kaplan–Meier survival analysis tested the differences among patients with different concurrent mutations. ctDNA test was administered before and after treatment and its correlation with efficacy. Results A total of 38 patients were enrolled, with co-mutations in TP53 (76.3%), PIK3CA (26.3%), and RB1 (2.6%). With a median follow-up of 25.6 months, the median progression-free survival (PFS) was 29.0 months (95% CI,18.6–NR), and 1-year PFS rate was 85% (95% CI, 70.4–94.5%). Objective response rate was 73.7% (95% CI, 56.9–86.3%), and disease control rate was 97.4% (95% CI, 85.8–99.9%). Adverse events of any grade occurred in all patients. Seven (18.4%) patients experienced grade 3 treatment-related adverse events (TRAEs), with no grade 4 TRAEs or treatment-related deaths. Conclusion Osimertinib plus anlotinib shows promising efficacy and manageable toxicity as first-line treatment for advanced NSCLC with EGFR co-mutations (ChiCTR2300070023). Clinical trial registration This study was registered in the Chinese Clinical Trial Registry (ChiCTR) under the registration number ChiCTR2300070023 on March 31, 2023 (https://www.chictr.org.cn).