Adjuvant therapy in completely resected, EGFR-mutant non-small cell lung cancer: a comparative analysis of treatment efficacy between EGFR-TKI and anti-PD-1/PD-L1 immunotherapy

Abstract

The IMpower010 and KEYNOTE-091 trials have demonstrated the benefit of adjuvant immunotherapy (IO) after chemotherapy (C+IO) in resected non-small cell lung cancer (NSCLC), including those with epidermal growth factor receptor gene (EGFR) mutation. Meanwhile, several studies have reported that EGFR-tyrosine kinase inhibitor (EGFR-TKI) may prolong disease-free survival (DFS) in these patients. However, there is currently a lack of head-to-head comparison between these two adjuvant therapy strategies. Therefore, we designed a comparative analysis of their efficacy to inform clinical decision-making by assessing DFS as the primary outcome. The results of direct meta-analysis indicated that EGFR-TKI reduced the risk of recurrence and/or death in completely resected NSCLC (HR_{EGFR-TKI/chemo} = 0.41, 95% CI: 0.23 to 0.74, p=0.003), while C+IO did not significantly improve DFS compared with chemotherapy alone (HR_C+IO/chemo=0.68, 95% CI: 0.31 to 1.50, p=0.338). Indirect comparison suggested that EGFR-TKI has a trend to prolong DFS compared with C+IO (HR _{EGFR-TKI/C+IO} = 0.60, 95% CI: 0.23 to 1.61, p=0.312), while the third-generation TKI (3^rd-TKI) osimertinib significantly outperformed C+IO (HR_{3^rd-TKI/C+IO} = 0.29, 95% CI: 0.12 to 0.70, p=0.006). In conclusion, osimertinib rather than immunotherapy should be regarded as the preferred adjuvant therapy in completely resected, EGFR-mutant NSCLC.

Keywords: Adjuvant Drug Therapy; Immune Checkpoint Inhibitors; Non-Small Cell Lung Cancer.