Perioperative Durvalumab for Resectable NSCLC: Updated Outcomes for Japanese Patients in AEGEAN

In the phase 3 AEGEAN study, perioperative durvalumab plus neoadjuvant chemotherapy significantly improved the primary endpoints of event-free survival (EFS) and pathological complete response (pCR) in patients with resectable NSCLC versus neoadjuvant chemotherapy alone. We report prespecified exploratory Japanese subgroup analyses of EFS, disease-free survival (DFS), and overall survival (OS) (interim analyses; data cut-off [DCO] May 10, 2024); pCR (final analysis; DCO November 10, 2022); and safety. In this double-blind, placebo-controlled study, 79 treatment-naïve Japanese patients (stage II-IIIB[N2]) were randomized (1:1) to neoadjuvant chemotherapy plus durvalumab/placebo (every 3 weeks [Q3W], 4 cycles) pre-surgery, then adjuvant durvalumab/placebo (Q4W, 12 cycles). Efficacy was analyzed in the modified intention-to-treat population (N = 64; durvalumab arm n = 30, placebo arm n = 34), which excluded patients with documented EGFR/ALK aberrations. At the corresponding data cutoffs, EFS benefit favored the durvalumab arm (unstratified HR, 0.63; 95% CI, 0.26-1.45; median follow-up, 42 months [censored patients]), and the pCR rate was numerically higher with durvalumab versus placebo (33.3% vs. 5.9%). A clinically meaningful DFS improvement favored the durvalumab arm (unstratified HR 0.47, 95% CI 0.16-1.21); however, no difference in OS was observed (unstratified HR 1.01, 95% CI 0.40-2.51). Grade 3/4 adverse events occurred in 62.2% and 65.9% of patients with durvalumab and placebo, respectively. Improvements in EFS and pCR with perioperative durvalumab plus neoadjuvant chemotherapy versus neoadjuvant chemotherapy alone were comparable to, or greater than, those observed in the global study population, supporting this regimen as a treatment option for Japanese patients. Trial Registration: ClinicalTrials.Gov Identifier NCT03800134.