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Neoadjuvant durvalumab plus radiation versus durvalumab alone in stages I–III non-small cell lung cancer: survival outcomes and molecular correlates of a randomized phase II trial

Author

Listed:
  • Nasser K. Altorki

    (Weill Cornell Medicine, Department of Cardiothoracic Surgery)

  • Zachary H. Walsh

    (Columbia University Irving Medical Center, Vagelos College of Physicians & Surgeons)

  • Johannes C. Melms

    (Columbia University Irving Medical Center, Vagelos College of Physicians & Surgeons)

  • Jeffery L. Port

    (Weill Cornell Medicine, Department of Cardiothoracic Surgery)

  • Benjamin E. Lee

    (Weill Cornell Medicine, Department of Cardiothoracic Surgery)

  • Abu Nasar

    (Weill Cornell Medicine, Department of Cardiothoracic Surgery)

  • Cathy Spinelli

    (Weill Cornell Medicine, Department of Cardiothoracic Surgery)

  • Lindsay Caprio

    (Columbia University Irving Medical Center, Vagelos College of Physicians & Surgeons)

  • Meri Rogava

    (Columbia University Irving Medical Center, Vagelos College of Physicians & Surgeons)

  • Patricia Ho

    (Columbia University Irving Medical Center, Vagelos College of Physicians & Surgeons)

  • Paul J. Christos

    (Weill Cornell Medicine)

  • Ashish Saxena

    (Weill Cornell Medicine, Division of Hematology and Oncology)

  • Olivier Elemento

    (Weill Cornell Medicine, Caryl and Israel Englander Institute for Precision Medicine, Institute for Computational Biomedicine, Department of Physiology and Biophysics)

  • Bhavneet Bhinder

    (Weill Cornell Medicine, Caryl and Israel Englander Institute for Precision Medicine, Institute for Computational Biomedicine, Department of Physiology and Biophysics)

  • Casey Ager

    (Columbia University Irving Medical Center, Vagelos College of Physicians & Surgeons)

  • Amit Dipak Amin

    (Columbia University Irving Medical Center, Vagelos College of Physicians & Surgeons)

  • Nicholas J. Sanfilippo

    (Weill Cornell Medicine, Department of Radiation Oncology)

  • Vivek Mittal

    (Weill Cornell Medicine, Department of Cardiothoracic Surgery)

  • Alain C. Borczuk

    (Department of Pathology, Northwell Health, Greenvale)

  • Silvia C. Formenti

    (Weill Cornell Medicine, Department of Radiation Oncology)

  • Benjamin Izar

    (Columbia University Irving Medical Center, Vagelos College of Physicians & Surgeons
    Deparmtent of Systems Biology, Program for Mathematical Genomics, Columbia University
    Columbia Center for Translational Immunology)

  • Timothy E. McGraw

    (Weill Cornell Medicine, Department of Biochemistry)

Abstract

We previously reported the results of a randomized phase II trial (NCT02904954) in patients with early-stage non-small cell lung cancer (NSCLC) who were treated with either two preoperative cycles of the anti-PD-L1 antibody durvalumab alone or combined with immunomodulatory doses of stereotactic radiation (DRT). The trial met its primary endpoint of major pathological response, which was significantly higher following DRT with no new safety signals. Here, we report on the prespecified secondary endpoint of disease-free survival (DFS) regardless of treatment assignment and the prespecified exploratory analysis of DFS in each arm of the trial. DFS at 2 and 3 years across patients in both arms of the trial were 73% (95% CI: 62.1–84.5) and 65% (95% CI: 52.5–76.9) respectively. For the exploratory endpoint of DFS in each arm of the trial, three-year DFS was 63% (95% CI: 46.0–80.4) in the durvalumab monotherapy arm compared to 67% (95% CI: 49.6–83.4) in the dual therapy arm. In addition, we report post hoc exploratory analysis of progression-free survival as well as molecular correlates of response and recurrence through high-plex immunophenotyping of sequentially collected peripheral blood and gene expression profiles from resected tumors in both treatment arms. Together, our results contribute to the evolving landscape of neoadjuvant treatment regimens for NSCLC and identify easily measurable potential biomarkers of response and recurrence.

Suggested Citation

  • Nasser K. Altorki & Zachary H. Walsh & Johannes C. Melms & Jeffery L. Port & Benjamin E. Lee & Abu Nasar & Cathy Spinelli & Lindsay Caprio & Meri Rogava & Patricia Ho & Paul J. Christos & Ashish Saxen, 2023. "Neoadjuvant durvalumab plus radiation versus durvalumab alone in stages I–III non-small cell lung cancer: survival outcomes and molecular correlates of a randomized phase II trial," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44195-x
    DOI: 10.1038/s41467-023-44195-x
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    1. Claire Vanpouille-Box & Amandine Alard & Molykutty J. Aryankalayil & Yasmeen Sarfraz & Julie M. Diamond & Robert J. Schneider & Giorgio Inghirami & C. Norman Coleman & Silvia C. Formenti & Sandra Dema, 2017. "DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity," Nature Communications, Nature, vol. 8(1), pages 1-15, August.
    2. Thomas Duhen & Rebekka Duhen & Ryan Montler & Jake Moses & Tarsem Moudgil & Noel F. de Miranda & Cheri P. Goodall & Tiffany C. Blair & Bernard A. Fox & Jason E. McDermott & Shu-Ching Chang & Gary Grun, 2018. "Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
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