Adjuvant chemotherapy before osimertinib in EGFR-mutated stage IB lung adenocarcinoma: a clinical dilemma

Background: The ADAURA trial demonstrated the efficacy of adjuvant osimertinib in patients with resected, early-stage, epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, the role of adjuvant chemotherapy followed by osimertinib for patients with high-risk, EGFR-mutant stage IB (<4 cm) adenocarcinoma remains unclear. The aim of this study is to evaluate the efficacy of adjuvant chemotherapy in these patients. Methods: This retrospective study analyzed the medical records of patients with pathologic stage IB (T2aN0M0, <4 cm) EGFR-mutant adenocarcinoma of the lung who had high-risk factors and underwent surgical resection between January 2010 and January 2017. We evaluated the clinical impact of adjuvant chemotherapy and analyzed risk factors associated with recurrence-free survival (RFS) and overall survival (OS). Results: Of the 178 patients, 42 (23.6%) and 136 (76.4%) were in the adjuvant chemotherapy and non-adjuvant chemotherapy groups, respectively. Median RFS was 55 and 97 months in the adjuvant chemotherapy and non-adjuvant chemotherapy groups, respectively (P=0.22). Notably, 2-, 5-, and 10-year RFS rates were 71.4%, 49.9%, and 35.7% for the adjuvant chemotherapy group and 78.9%, 57.3%, and 49.9% for the non-adjuvant chemotherapy group, respectively. Multivariate analysis identified age ≥60 years, lymphovascular invasion, and micropapillary/solid predominant patterns as independent predictors of recurrence. Conversely, overweight patients (body mass index ≥25 kg/m2) had a lower risk of recurrence. Median OS was 134 and 145 months in the adjuvant chemotherapy and non-adjuvant chemotherapy groups, respectively (P=0.84). Multivariate analysis identified age ≥60 years and micropapillary/solid predominant patterns as independent predictors of OS. Conclusions: The efficacy of adjuvant chemotherapy in patients with stage IB (<4 cm) EGFR-mutant adenocarcinoma and high-risk features remains uncertain.