Surgical Outcomes with Neoadjuvant Durvalumab Plus Chemotherapy Followed by Adjuvant Durvalumab in Resectable NSCLC

INTRODUCTION: In AEGEAN, perioperative durvalumab plus neoadjuvant chemotherapy, versus neoadjuvant chemotherapy alone, significantly improved event-free survival and pathological complete response (primary endpoints; modified ITT [mITT] population, which excluded patients with known EGFR/ALK aberrations) with a manageable safety profile in patients with resectable (R)-NSCLC. Here, we report surgical outcomes from AEGEAN. METHODS: Patients with treatment-naïve R-NSCLC (stage II-IIIB[N2]) and ECOG PS 0/1 were randomized (1:1) to platinum-based chemotherapy plus durvalumab or placebo IV (Q3W, 4 cycles) before surgery, followed by durvalumab or placebo (Q4W, 12 cycles). Surgical outcomes were summarized for the mITT population using descriptive statistics. RESULTS: 737/740 mITT patients received treatment, 366 and 371 in the durvalumab and placebo arms, respectively; 80.6% and 80.7% underwent surgery, 77.6% and 76.7% completed surgery, and, of the 295 and 302 patients who underwent surgery, 17.3% and 22.2% had delayed surgery. Median time from last neoadjuvant dose to surgery was 34.0 days in both arms. Of patients who underwent surgery, similar proportions had open (49.2% vs 50.7%) and minimally invasive (49.2% vs 47.0%) procedures; lobectomy was the most common procedure (88.1% vs 85.4%). R0 resection rates were numerically higher in the durvalumab versus placebo arm (94.7% vs 91.3%). Median time from surgery to first adjuvant dose was 50.0 versus 52.0 days. In exploratory analyses, a numerically higher proportion of patients in the durvalumab versus placebo arm with baseline N2 nodal status had downstaging from N2 to N0 (47.3% vs 40.2%) or, with baseline N1 nodal status, from N1 to N0 (53.6% vs 46.2%) after surgery. Similar proportions had surgical complication(s) (59.1% vs 60.1%), primarily grade 1/2 (53.0% vs 51.8%, modified safety analysis set). CONCLUSION: The addition of durvalumab to neoadjuvant chemotherapy had no detrimental effect on the feasibility, approach, type, or timing of surgery and was associated with a tolerable surgical safety profile, versus neoadjuvant chemotherapy alone. GOV IDENTIFIER: NCT03800134.

• Mitsudomi, T.
• Heymach, J. V.
• Reck, M.
• Taube, J. M.
• Gao, S.
• Horio, Y.
• You, J.
• Li, G.
• Van Luong, D.
• Saeteng, S.
• Tanaka, F.
• Watzka, S. B.
• Urban, L.
• Szalai, Z.
• Akamatsu, H.
• Kang, J. H.
• Orlandi, F. J.
• Mukhametshina, G. Z.
• Pircher, A.
• Andrade Teixeira, C. H.
• Aperghis, M.
• Doherty, G. J.
• Doake, R.
• Fouad, T. M.
• Harpole, D.