Immunotherapy plus Chemotherapy for Patients with EGFR-Mutated Non-Squamous Cell Lung Cancer for Disease Progression after EGFR Tyrosine-Kinase Inhibitor: A Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations face poor outcomes after progression on tyrosine kinase inhibitors (TKIs). The efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in these patients remains uncertain. Methods: We searched for studies published between randomized controlled trials of ICIs in combination therapies in advanced NSCLC patients post EGFR TKI progression. Data on progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were extracted and analyzed. Results: Six studies with a total of 2,225 patients were analyzed. The pooled hazard ratio (HR) for PFS was 0.60 (95% CI, 0.55 - 0.65; P < 0.0001), indicating a significant improvement in PFS with ICIs. Subgroup analysis suggested that patients with prior exposure to third-generation TKIs showed a more pronounced benefit (HR = 0.61; 95% CI, 0.49 - 0.76; P < 0.0001). However, no benefit was found in patients without prior exposure. The efficacy of the experimental interventions was also shown on the pooled estimates of OS (HR = 0.87; 95% CI, 0.77 – 0.0.99; P value = 0.04) and ORR (OR = 1.91; 95% CI, 1.32 – 2.76; P <0.0001). Conclusions: ICIs may significantly benefit PFS among patients with EGFR-mutated NSCLC who have progressed on TKI treatment. Future research should continue stratifying patients based on prior treatment exposure to optimize therapeutic strategies.