John V Heymach, Jie He, David Harpole, Tetsuya Mitsudomi, Janis M Taube, Shugeng Gao, Laszlo Urban, Jin Hyoung Kang, Francisco J Orlandi, Jeronimo Rodriguez-Cid, Bartomeu Massuti, Luis Leon Mateos, Giulia Pasello, Quincy Chu, Jaroslaw Kolb-Sielecki, Masao Nakata, Gabriella Galffy, Maximilian Hochmair, Thomas Winder, Ruslan Zukov, Gabriel Garbaos, Yoshitsugu Horio, Gyula Ostoros, Tho V Tran, Jian You, Kang-Yun Lee, Lorenzo Antonuzzo, Hiroaki Akamatsu, Bivas Biswas, Alexander Spira, Jeffrey Crawford, Ha T Le, Mike Aperghis, Helen Mann, Tamer M Fouad, Gary J Doherty, Martin Reck
In AEGEAN, perioperative durvalumab plus neoadjuvant chemotherapy, versus neoadjuvant chemotherapy alone, significantly improved event-free survival (EFS) and pathologic complete response in patients with resectable non-small cell lung cancer (R-NSCLC), with a safety profile consistent with the individual agents. We report EFS from a second planned interim analysis, interim disease-free survival (DFS) and overall survival (OS), and safety, after all patients completed/discontinued treatment. In this phase III, double-blind, placebo-controlled study, patients with treatment-naïve R-NSCLC (stage II-IIIB [N2]) were randomly assigned (1:1) to neoadjuvant platinum-based chemotherapy plus durvalumab/placebo (once every 3 weeks, four cycles) presurgery and then adjuvant durvalumab/placebo (once every 4 weeks, 12 cycles). Efficacy was analyzed in the modified intention-to-treat population (n = 740; for DFS, its resected subpopulation), which excluded patients with documented EGFR/ALK aberrations. As of May 10, 2024 (median follow-up, 25.9 months [censored patients]), EFS benefit favoring the durvalumab arm remained consistent (hazard ratio [HR], 0.69 [95% CI, 0.55 to 0.88]). Numerical improvement in DFS (HR, 0.66 [95% CI, 0.47 to 0.92]) and OS (HR, 0.89 [95% CI, 0.70 to 1.14]) favored the durvalumab arm. Maximum grade 3/4 adverse events occurred in 15.4% and 10.6% of the durvalumab and placebo arms, respectively, during adjuvant treatment. These results further support perioperative durvalumab plus neoadjuvant chemotherapy as a new treatment option.