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Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer.

John V Heymach1, David Harpole1, Tetsuya Mitsudomi1

  • 1From the Department of Thoracic-Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston (J.V.H.), and US Oncology Research, the Woodlands (A.S.) - both in Texas; the Department of Surgery, Duke University Medical Center (D.H.), and Duke Cancer Institute (J.C.) - both in Durham, NC; the Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama (T.M.), the Department of Thoracic Surgery, Aichi Cancer Center Hospital, Aichi (H.K.), and Internal Medicine III, Wakayama Medical University, Wakayama (H.A.) - all in Japan; the Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Kimmel Cancer Center, Baltimore (J.M.T.); Törökbalint Institute of Pulmonology, Törökbálint (G. Galffy), Koranyi National Institute for TB and Pulmonology, Budapest (G.O.), and the University Teaching Hospital of Fejér County, Székesfehérvár (Z.P.-S.) - all in Hungary; the Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna (M.H.), and the Department of Hematology, Oncology, Gastroenterology and Infectiology, Landeskrankenhaus Feldkirch, Feldkirch (T.W.) - both in Austria; Krasnoyarsk State Medical University, Krasnoyarsk, Russia (R.Z.); Fundación Estudios Clínicos, Santa Fe, Argentina (G. Garbaos); the Thoracic Surgery Department, National Cancer Center-National Clinical Research Center for Cancer-Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (S.G.), and the Department 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 (J.Y.) - both in China; the Oncology and Chemotherapy Department, University Medical Center of Ho Chi Minh City, Ho Chi Minh City (T.V.T.), and No. 1 Medical Oncology Department, Hanoi Oncology Hospital, Hanoi (H.T.L.) - both in Vietnam; the Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan (K.-Y.L.); the Clinical Oncology Unit, Careggi University Hospital, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy (L.A.); Tata Medical Center, Kolkata, India (B.B.); Virginia Cancer Specialists Research Institute, Fairfax (A.S.); AstraZeneca, Cambridge, United Kingdom (M.A., G.J.D., H.M.); AstraZeneca, New York (T.M.F.); and Lung Clinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.).

The New England Journal of Medicine
|October 23, 2023
PubMed
Summary

Perioperative durvalumab combined with chemotherapy significantly improved event-free survival and pathological complete response in resectable non-small-cell lung cancer (NSCLC) patients. This immunotherapy approach demonstrated a favorable safety profile, offering a new treatment option.

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Area of Science:

  • Oncology
  • Immunotherapy
  • Thoracic Surgery

Background:

  • Neoadjuvant or adjuvant immunotherapy enhances outcomes in resectable non-small-cell lung cancer (NSCLC).
  • Perioperative immunotherapy regimens aim to combine neoadjuvant and adjuvant benefits for improved long-term patient outcomes.
  • Investigating the efficacy of perioperative durvalumab in conjunction with chemotherapy for resectable NSCLC.

Purpose of the Study:

  • To evaluate the impact of perioperative durvalumab plus chemotherapy on event-free survival (EFS) in patients with resectable NSCLC.
  • To assess the pathological complete response (pCR) rates in patients receiving perioperative durvalumab compared to placebo.
  • To determine the safety and tolerability of the perioperative durvalumab regimen.

Main Methods:

  • A randomized trial assigned 802 patients with resectable NSCLC (Stage II-IIIB) to receive platinum-based chemotherapy plus durvalumab or placebo.
  • Treatment involved 4 cycles of neoadjuvant therapy followed by 12 cycles of adjuvant therapy, with randomization stratified by stage and PD-L1 expression.
  • Primary endpoints included event-free survival and pathological complete response, with efficacy and safety data analyzed.

Main Results:

  • Durvalumab significantly improved EFS, with a hazard ratio of 0.68 for disease progression, recurrence, or death (P=0.004).
  • At 12 months, EFS was 73.4% with durvalumab versus 64.5% with placebo; pCR was significantly higher (17.2% vs. 4.3%, P<0.001).
  • Benefits were observed across stages and PD-L1 expression levels, with similar Grade 3/4 adverse event rates (42.4% vs. 43.2%).

Conclusions:

  • Perioperative durvalumab plus neoadjuvant chemotherapy significantly enhances EFS and pCR in resectable NSCLC compared to chemotherapy alone.
  • The safety profile of perioperative durvalumab is consistent with its individual agents, supporting its clinical utility.
  • This perioperative immunotherapy strategy represents a promising advancement for patients with resectable NSCLC.