Background: Recent studies have demonstrated benefits from adjuvant tyrosine-kinase inhibitors (TKIs) compared with chemotherapy in non-small cell lung cancer. We launched a multi-center retrospective study to evaluate the efficacy and toxicity of adjuvant TKIs with or without chemotherapy in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma.
Methods: Two hundred and seventy-four consecutive cases with stage III-pN2 lung adenocarcinoma and complete resection have been investigated. Clinic-pathologic characteristics, adjuvant treatments, long-term survivals, and toxicities were documented. Risk factors of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated.
Results: There were 52 (19.0%) patients treated with adjuvant TKIs alone, 199 (72.6%) with adjuvant chemotherapy alone, and 23 (8.4%) with both. After a median follow-up time of 29 months, the two-year DMFS, DFS, and OS was 61.2%, 54.1%, and 91.2%, respectively. According to univariable analyses, the risk factors were lymphovascular invasion (p < 0.001), extranodal extension (p = 0.005), and adjuvant systemic therapy (p = 0.006) for DMFS, EGFR mutation type (p = 0.025), lymphovascular invasion (p = 0.013), extranodal extension (p = 0.004), and adjuvant systemic therapy (p < 0.001) for DFS, and EGFR mutation type (p < 0.001) for OS. Multivariable analyses indicated that the independent prognostic factors were adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, Harzard ratio (HR) = 0.40; p = 0.036; TKIs vs. chemotherapy, HR = 0.38; p = 0.004), lymphovascular invasion (yes vs. no, HR = 2.22; p = 0.001) for DMFS, and adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, HR = 0.42; p = 0.034; TKIs vs. chemotherapy, HR = 0.33; p < 0.001) for DFS. No significant difference was found in the incidence of Grade 3-4 toxicities between groups (p = 0.445).
Conclusions: Adjuvant TKIs might be a beneficial choice compared with adjuvant chemotherapy or combination systemic treatments.
Keywords: EGFR mutation; N2; adjuvant TKIs; chemotherapy; lung adenocarcinoma.