Atezolizumab Combined With Cisplatin Plus Vinorelbine as Adjuvant Therapy for Completely Resected NSCLC With EGFR Mutation (West Japan Oncology Group 11719L: ADJUST Study)

Introduction: The benefit of adjuvant EGFR tyrosine kinase inhibitors in resected EGFR-mutated NSCLC is limited by recurrence, and the role of immune checkpoint inhibitors remains unclear. We evaluated atezolizumab combined with cisplatin and vinorelbine as adjuvant therapy in completely resected EGFR-mutated NSCLC. Methods: In a single-arm, multicenter phase II trial, patients with completely resected stage II to IIIA NSCLC harboring EGFR exon 19 deletion or L858R mutations received four cycles of atezolizumab with cisplatin and vinorelbine, followed by up to 12 months of atezolizumab maintenance. The primary end point was the 2-year disease-free survival (DFS) rate. Propensity score-matched patients from the phase III IMPACT trial (cisplatin + vinorelbine) served as an external control. Exploratory biomarkers included tumor mutational burden (TMB) and immune gene expression profiling. Results: The 2-year DFS rate was 44.4% (lower limit of the one-sided 90% confidence interval: 29.4%). The median DFS was 21.1 months with atezolizumab in ADJUST versus 17.7 months in matched controls from IMPACT. Overall survival was not reached in either group. The median TMB was 5.1 mutations per megabase; 17% were TMB-high (≥10 mutations per megabase). RNA profiling suggested that immune-pathway enrichment may be associated with longer DFS. Immune-related adverse events were manageable, and no fatal events occurred. Conclusions: Adjuvant atezolizumab with cisplatin and vinorelbine did not significantly improve DFS compared with patients with resected EGFR-mutated NSCLC. These results highlight the limited benefit of immune checkpoint inhibitors in this population and the need for predictive biomarkers to guide immunotherapy strategies for improving cure rates.