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Efficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer

Author

Listed:
  • Lingzhi Hong

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Muhammad Aminu

    (The University of Texas MD Anderson Cancer Center)

  • Shenduo Li

    (Division of Hematology and Oncology, Mayo Clinic)

  • Xuetao Lu

    (The University of Texas MD Anderson Cancer Center)

  • Milena Petranovic

    (Massachusetts General Hospital)

  • Maliazurina B. Saad

    (The University of Texas MD Anderson Cancer Center)

  • Pingjun Chen

    (The University of Texas MD Anderson Cancer Center)

  • Kang Qin

    (The University of Texas MD Anderson Cancer Center)

  • Susan Varghese

    (The University of Texas MD Anderson Cancer Center)

  • Waree Rinsurongkawong

    (The University of Texas MD Anderson Cancer Center)

  • Vadeerat Rinsurongkawong

    (The University of Texas MD Anderson Cancer Center)

  • Amy Spelman

    (The University of Texas MD Anderson Cancer Center)

  • Yasir Y. Elamin

    (The University of Texas MD Anderson Cancer Center)

  • Marcelo V. Negrao

    (The University of Texas MD Anderson Cancer Center)

  • Ferdinandos Skoulidis

    (The University of Texas MD Anderson Cancer Center)

  • Carl M. Gay

    (The University of Texas MD Anderson Cancer Center)

  • Tina Cascone

    (The University of Texas MD Anderson Cancer Center)

  • Saumil J. Gandhi

    (The University of Texas MD Anderson Cancer Center)

  • Steven H. Lin

    (The University of Texas MD Anderson Cancer Center)

  • Percy P. Lee

    (The University of Texas MD Anderson Cancer Center)

  • Brett W. Carter

    (The University of Texas MD Anderson Cancer Center)

  • Carol C. Wu

    (The University of Texas MD Anderson Cancer Center)

  • Mara B. Antonoff

    (The University of Texas MD Anderson Cancer Center)

  • Boris Sepesi

    (The University of Texas MD Anderson Cancer Center)

  • Jeff Lewis

    (The University of Texas MD Anderson Cancer Center)

  • Don L. Gibbons

    (The University of Texas MD Anderson Cancer Center)

  • Ara A. Vaporciyan

    (The University of Texas MD Anderson Cancer Center)

  • Xiuning Le

    (The University of Texas MD Anderson Cancer Center)

  • J. Jack Lee

    (The University of Texas MD Anderson Cancer Center)

  • Sinchita Roy-Chowdhuri

    (The University of Texas MD Anderson Cancer Center)

  • Mark J. Routbort

    (The University of Texas MD Anderson Cancer Center)

  • Justin F. Gainor

    (Massachusetts General Hospital)

  • John V. Heymach

    (The University of Texas MD Anderson Cancer Center)

  • Yanyan Lou

    (Division of Hematology and Oncology, Mayo Clinic)

  • Jia Wu

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Jianjun Zhang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Natalie I. Vokes

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

Abstract

The role of combination chemotherapy with immune checkpoint inhibitors (ICI) (ICI-chemo) over ICI monotherapy (ICI-mono) in non-small cell lung cancer (NSCLC) remains underexplored. In this retrospective study of 1133 NSCLC patients, treatment with ICI-mono vs ICI-chemo associate with higher rates of early progression, but similar long-term progression-free and overall survival. Sequential vs concurrent ICI and chemotherapy have similar long-term survival, suggesting no synergism from combination therapy. Integrative modeling identified PD-L1, disease burden (Stage IVb; liver metastases), and STK11 and JAK2 alterations as features associate with a higher likelihood of early progression on ICI-mono. CDKN2A alterations associate with worse long-term outcomes in ICI-chemo patients. These results are validated in independent external (n = 89) and internal (n = 393) cohorts. This real-world study suggests that ICI-chemo may protect against early progression but does not influence overall survival, and nominates features that identify those patients at risk for early progression who may maximally benefit from ICI-chemo.

Suggested Citation

  • Lingzhi Hong & Muhammad Aminu & Shenduo Li & Xuetao Lu & Milena Petranovic & Maliazurina B. Saad & Pingjun Chen & Kang Qin & Susan Varghese & Waree Rinsurongkawong & Vadeerat Rinsurongkawong & Amy Spe, 2023. "Efficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36328-z
    DOI: 10.1038/s41467-023-36328-z
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    References listed on IDEAS

    as
    1. Jacqulyne P. Robichaux & Xiuning Le & R. S. K. Vijayan & J. Kevin Hicks & Simon Heeke & Yasir Y. Elamin & Heather Y. Lin & Hibiki Udagawa & Ferdinandos Skoulidis & Hai Tran & Susan Varghese & Junqin H, 2021. "Structure-based classification predicts drug response in EGFR-mutant NSCLC," Nature, Nature, vol. 597(7878), pages 732-737, September.
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    3. Shom Goel & Molly J. DeCristo & April C. Watt & Haley BrinJones & Jaclyn Sceneay & Ben B. Li & Naveed Khan & Jessalyn M. Ubellacker & Shaozhen Xie & Otto Metzger-Filho & Jeremy Hoog & Matthew J. Ellis, 2017. "CDK4/6 inhibition triggers anti-tumour immunity," Nature, Nature, vol. 548(7668), pages 471-475, August.
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