Surgical Outcomes With Neoadjuvant Durvalumab Plus Chemotherapy Followed by Adjuvant Durvalumab in Resectable NSCLC
- PMID: 40545237
- DOI: 10.1016/j.jtho.2025.06.015
Surgical Outcomes With Neoadjuvant Durvalumab Plus Chemotherapy Followed by Adjuvant Durvalumab in Resectable NSCLC
Abstract
Introduction: In AEGEAN, perioperative durvalumab plus neoadjuvant chemotherapy, versus neoadjuvant chemotherapy alone, significantly improved event-free survival (p = 0.004) and pathologic complete response (p < 0.001; primary end points; modified intention-to-treat [mITT] population, which excluded patients with known EGFR or ALK aberrations) with a manageable safety profile in patients with resectable (R)-NSCLC. Here, we report surgical outcomes from AEGEAN.
Methods: Patients with treatment-naive R-NSCLC (stage II-IIIB [N2]) and Eastern Cooperative Oncology Group performance status 0 or 1 were randomized (1:1) to platinum-based chemotherapy plus durvalumab or placebo intravenously (every 3 wk, 4 cycles) before surgery, followed by durvalumab or placebo (every 4 wk, 12 cycles). Surgical outcomes were summarized for the mITT population using descriptive statistics.
Results: A total of 737 out of 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. The median time from last neoadjuvant dose to surgery was 34.0 days in both arms. Of the patients who underwent surgery, similar proportions had open (49.2% versus 50.7%) and minimally invasive (49.2% versus 47.0%) procedures; lobectomy was the most common procedure (88.1% versus 85.4%). R0 resection rates were numerically higher in the durvalumab versus placebo arm (94.7% versus 91.3%). The 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% versus 40.2%) or, with baseline N1 nodal status, from N1 to N0 (53.6% versus 46.2%) after surgery. Similar proportions had surgical complication(s) (59.1% versus 60.1%), primarily grade 1 or 2 (53.0% versus 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.
Clinical trial information: ClinicalTrials.Gov Identifier: NCT03800134.
Keywords: Durvalumab; Non–small-cell lung cancer; Perioperative; Surgical outcomes.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Disclosures Prof. Mitsudomi has received grants or contracts from Boehringer Ingelheim, AstraZeneca, Taiho, and BridgeBio Pharma; honoraria from AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceuticals, Pfizer, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Merck, Ono Pharmaceuticals, Amgen, and Daiichi Sankyo; and has participated on an advisory board or committee for Regeneron, Bristol Myers Squibb, Janssen, and Taiho. Dr. Heymach has participated on an advisory board or committee for AstraZeneca, Boehringer Ingelheim, Catalyst, Genentech, GlaxoSmithKline, Guardant Health, Foundation Medicine, Hengrui Therapeutics, Eli Lilly, Novartis, Spectrum, EMD Serono, Sanofi, Takeda, Mirati Therapeutics, Bristol Myers Squibb, BrightPath Biotherapeutics, Janssen Global Services, Nexus Health Systems, Pneuma Respiratory, Kairos Venture Investments, Roche, and Leads Biolabs; and received other research support from AstraZeneca, GlaxoSmithKline, Spectrum, Takeda, and Boehringer Ingelheim. Prof. Reck has received consulting fees from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Beigene, Daiichi Sankyo, GlaxoSmithKline, Lilly, Merck, Merck Sharp & Dohme, Novartis, Pierre Fabre, Pfizer, Regeneron, and Roche; honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Beigene, Daiichi Sankyo, GlaxoSmithKline, Lilly, Merck, Merck Sharp & Dohme, Novartis, Pierre Fabre, Pfizer, Regeneron, and Roche; and travel support from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Beigene, Daiichi Sankyo, GlaxoSmithKline, Lilly, Merck, Merck Sharp & Dohme, Novartis, Pierre Fabre, Pfizer, Regeneron, and Roche. Janis M. Taube has participated on an advisory board for AstraZeneca, Bristol Myers Squibb, Merck, Regeneron, Elephas, Lunaphore, Roche, and Moderna; and has received research grants from Bristol Myers Squibb and Akoya Biosciences. Dr. Horio has received grants or contracts from AstraZeneca, AbbVie, Chugai, Amgen, Eli Lilly, Merck Sharp & Dohme, and Merck Serono; and honoraria from AstraZeneca, Merck Sharp & Dohme, and Chugai. Dr. Tanaka has received grants or contracts from Boehringer Ingelheim Japan, Ono Pharmaceutical, Taiho Pharmaceutical, Eli Lilly Japan, Chugai Pharmaceutical; consulting fees from AstraZeneca, Chugai Pharmaceutical, and Ono Pharmaceutical; and honoraria from Merck Sharp & Dohme, Bristol Myers Squibb, Boehringer Ingelheim Japan, Ono Pharmaceutical, Johnson & Johnson, Covidien Japan, Taiho Pharmaceutical, Eli Lilly Japan, AstraZeneca, Chugai Pharmaceutical, Kyowa-Kirin, Takeda Pharmaceutical, Pfizer, Olympus, Stryker, and Intuitive Japan. Dr. Watzka has received honoraria for speaker fees from AstraZeneca, Bristol Myers Squibb, and Merck Sharp & Dohme. Dr. Szalai has received consulting fees from AstraZeneca, Sanofi, and Berlin-Chemie; travel support from Berlin-Chemie, Chiesi, and Merck Sharp & Dohme; and has participated on an advisory board or committee for AstraZeneca, Sanofi, and Bristol Myers Squibb. Dr. Akamatsu has received grants or contracts from Amgen, Chugai Pharmaceutical, and Novartis; honoraria from Amgen, Boehringer Ingelheim Japan, Chugai Pharmaceutical, Merck Sharp & Dohme, Novartis, Pfizer, Taiho Pharmaceutical, AstraZeneca, Bristol Myers Squibb, Eli Lilly Japan, Nippon Kayaku, Ono Pharmaceutical, Takeda, Daiichi Sankyo; and has participated on an advisory board or committee for Amgen, Janssen, Sandoz, and Merck Sharp & Dohme. Dr. Kang has received grants or contracts from Bayer; consulting fees from Eli Lilly, Pfizer, Novartis, and Daiichi Sankyo; and honoraria from Roche, Boehringer Ingelheim, Bayer, and Yuhan; and has participated on an advisory board or committee for Boehringer Ingelheim, Novartis, AstraZeneca, and Yuhan. Prof. Orlandi has received grants or contracts from Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Gilead Kite, GlaxoSmithKline, Merck Sharp & Dohme, Pfizer, Regeneron, Roche, and Sanofi; and consulting fees from Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, and Roche; and has participated on an advisory board or committee for Bristol Myers Squibb, Merck Sharp & Dohme, and Sanofi. Dr. Pircher has received consulting fees and honoraria from, and participated on an advisory board or committee for, Merck Sharp & Dohme, Pfizer, Pierre Fabre, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Amgen, Johnson & Johnson, and Roche; and received grants from Merck Sharp & Dohme. Dr. Andrade Teixeira has received consulting fees from AstraZeneca and Merck Sharp & Dohme; travel support from Johnson; and has participated on an advisory board or committee for AstraZeneca and Bristol Myers Squibb. Drs. Aperghis, Doherty, and Fouad are employees of, and have stock or stock options with, AstraZeneca. Ms Doake is an employee of AstraZeneca. Dr. Harpole has received travel support from and has participated on an advisory board or committee for AstraZeneca. The remaining authors declare no conflict of interest.
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