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

Lingzhi Hong, Muhammad Aminu, Shenduo Li, Xuetao Lu, Milena Petranovic, Maliazurina B. Saad, Pingjun Chen, Kang Qin, Susan Varghese, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, Amy Spelman, Yasir Y. Elamin, Marcelo V. Negrao, Ferdinandos Skoulidis, Carl M. Gay, Tina Cascone, Saumil J. Gandhi, Steven H. Lin, Percy P. Lee, Brett W. Carter, Carol C. Wu, Mara B. Antonoff, Boris Sepesi, Jeff Lewis, Don L. Gibbons, Ara A. Vaporciyan, Xiuning Le, J. Jack Lee, Sinchita Roy-Chowdhuri, Mark J. Routbort, Justin F. Gainor, John V. Heymach, Yanyan Lou, Jia Wu, Jianjun Zhang () and Natalie I. Vokes ()
Additional contact information
Lingzhi Hong: 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
Jianjun Zhang: The University of Texas MD Anderson Cancer Center
Natalie I. Vokes: The University of Texas MD Anderson Cancer Center

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36328-z

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