Abstract CT005: AEGEAN: A phase 3 trial of neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab in patients with resectable NSCLC

  • John V. Heymach
    1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX;
  • David Harpole
    2Department of Surgery, Duke University Medical Center, Durham, NC;
  • Tetsuya Mitsudomi
    3Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan;
  • Janis M. Taube
    4Bloomberg–Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Kimmel Cancer Center, Baltimore, MD;
  • Gabriella Galffy
    5Pest County Pulmonology Hospital, Törökbálint, Hungary;
  • Maximilian Hochmair
    6Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna, Austria;
  • Thomas Winder
    7Department of Hematology, Oncology, Gastroenterology and Infectiology, Landeskrankenhaus Feldkirch, Feldkirch, Austria;
  • Ruslan Zukov
    8Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation;
  • Gabriel Garbaos
    9Fundación Estudios Clínicos, Santa Fe, Argentina;
  • Shugeng Gao
    10Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;
  • Hiroaki Kuroda
    11Department of Thoracic Surgery, Aichi Cancer Center Hospital, Aichi, Japan;
  • Jian You
    12Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China;
  • Kang-Yun Lee
    13Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan;
  • Lorenzo Antonuzzo
    14Clinical Oncology Unit, Careggi University Hospital, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy;
  • Mike Aperghis
    15AstraZeneca, Cambridge, United Kingdom;
  • Gary J. Doherty
    15AstraZeneca, Cambridge, United Kingdom;
  • Helen Mann
    15AstraZeneca, Cambridge, United Kingdom;
  • Tamer M. Fouad
    16AstraZeneca, New York, NY;
  • Martin Reck
    17Lung Clinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.

説明

<jats:title>Abstract</jats:title> <jats:p>Background: Recent trials have demonstrated the clinical benefit of immunotherapy in either the neoadjuvant or adjuvant resectable (R) NSCLC setting. AEGEAN (NCT03800134) is a randomized, double-blind, placebo (PBO)-controlled trial assessing neoadjuvant durvalumab (D) + chemotherapy (CT) followed by surgery (Sx) and adjuvant D in patients (pts) with R-NSCLC.</jats:p> <jats:p>Methods: Adults with treatment (Tx)-naïve R-NSCLC (stage II-IIIB[N2]; AJCC 8th ed) and ECOG PS 0/1 were randomized (1:1) to receive D 1500 mg or PBO IV + platinum-based CT (every 3 weeks [Q3W] for 4 cycles) before Sx, then further D 1500 mg or PBO IV (Q4W, up to 12 cycles). Pts were stratified by disease stage (II vs III) and PD-L1 tumor cell expression (&lt;1% vs ≥1%, Ventana SP263). Pts with documented EGFR/ALK aberrations were excluded from the modified intent-to-treat (mITT) population for efficacy analyses. The primary endpoints were pathological complete response (pCR), evaluated centrally, and event-free survival (EFS; using RECIST v1.1), evaluated by BICR. Safety was assessed in all pts who received ≥1 study Tx dose.</jats:p> <jats:p>Results: Between Jan 2, 2019, and Apr 19, 2022, 802 pts were randomized to the ITT population (n=740 in the mITT population) of whom 799 received Tx (D arm, n=400; PBO arm, n=399). Baseline characteristics were largely balanced (mITT). Overall, 84.7% in the D arm and 87.2% in PBO arm completed 4 cycles of platinum-doublet CT and 77.6% and 76.7%, respectively, completed Sx (mITT). As of Nov 10, 2022 (data cutoff), median EFS follow-up in censored pts was 11.7 months (mITT). The pCR rate was significantly higher and EFS significantly prolonged in the D vs PBO arms (mITT) (Table). In the safety analysis set, maximum grade 3/4 any-cause AEs occurred in 42.3% vs 43.4% in the D and PBO arms, respectively, during the overall Tx period.</jats:p> <jats:p>Conclusions: The AEGEAN trial met both of its primary endpoints of improved pCR and EFS. Perioperative D plus neoadjuvant CT was associated with a manageable safety profile.</jats:p> <jats:p>Clinical trial identification: NCT03800134 (release date: January 11, 2019) Endpoint D arm PBO arm Tx effect P value pCR n/N: 63/366 (17.2%) n/N: 16/374 (4.3%) Difference in pCR (95% CI), %: 13.0 (8.7-17.6)a 0.000036 (assessed at IA)b EFS n events/N: 98/366 (26.8%) n events/N: 138/374 (36.9%) HR (95% CI): 0.68 (0.53-0.88)d 0.003902e Median (95% CI), months: NR (31.9-NR)c Median (95% CI), months: 25.9 (18.9-NR)c aCIs by stratified Miettinen and Nurminen’s method. bStatistical significance was achieved at the IA (402 pts; data cutoff, Jan 14, 2022); no testing was performed at FA. The statistically significant p-value of 0.000036 was based on a Cochran-Mantel-Haenszel test. cKaplan-Meier method. dStratified Cox proportional hazards model. eStratified log-rank test. CI, confidence interval; FA, final analysis; HR, hazard ratio; IA, interim analysis; NR, not reached.</jats:p> <jats:p>Citation Format: John V. Heymach, David Harpole, Tetsuya Mitsudomi, Janis M. Taube, Gabriella Galffy, Maximilian Hochmair, Thomas Winder, Ruslan Zukov, Gabriel Garbaos, Shugeng Gao, Hiroaki Kuroda, Jian You, Kang-Yun Lee, Lorenzo Antonuzzo, Mike Aperghis, Gary J. Doherty, Helen Mann, Tamer M. Fouad, Martin Reck. AEGEAN: A phase 3 trial of neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab in patients with resectable NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT005.</jats:p>

収録刊行物

  • Cancer Research

    Cancer Research 83 (8_Supplement), CT005-CT005, 2023-05-29

    American Association for Cancer Research (AACR)

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