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; Natalie I. Vokes

doi:10.1038/s41467-023-36328-z

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. LeeBrett 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, Natalie I. Vokes

Hematology / Oncology / Cancer Center / Breast Clinic

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	695
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-36328-z
State	Published - Dec 2023

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-023-36328-z

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Hong, L., Aminu, M., Li, S., Lu, X., Petranovic, M., Saad, M. B., Chen, P., Qin, K., Varghese, S., Rinsurongkawong, W., Rinsurongkawong, V., Spelman, A., Elamin, Y. Y., Negrao, M. V., Skoulidis, F., Gay, C. M., Cascone, T., Gandhi, S. J., Lin, S. H., ... Vokes, N. I. (2023). Efficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer. Nature communications, 14(1), Article 695. https://doi.org/10.1038/s41467-023-36328-z

Hong, L, Aminu, M, Li, S, Lu, X, Petranovic, M, Saad, MB, Chen, P, Qin, K, Varghese, S, Rinsurongkawong, W, Rinsurongkawong, V, Spelman, A, Elamin, YY, Negrao, MV, Skoulidis, F, Gay, CM, Cascone, T, Gandhi, SJ, Lin, SH, Lee, PP, Carter, BW, Wu, CC, Antonoff, MB, Sepesi, B, Lewis, J, Gibbons, DL, Vaporciyan, AA, Le, X, Jack Lee, J, Roy-Chowdhuri, S, Routbort, MJ, Gainor, JF, Heymach, JV, Lou, Y, Wu, J, Zhang, J & Vokes, NI 2023, 'Efficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer', Nature communications, vol. 14, no. 1, 695. https://doi.org/10.1038/s41467-023-36328-z

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

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.",

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

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year = "2023",

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doi = "10.1038/s41467-023-36328-z",

language = "English (US)",

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T1 - Efficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer

AU - Hong, Lingzhi

AU - Aminu, Muhammad

AU - Li, Shenduo

AU - Lu, Xuetao

AU - Petranovic, Milena

AU - Saad, Maliazurina B.

AU - Chen, Pingjun

AU - Qin, Kang

AU - Varghese, Susan

AU - Rinsurongkawong, Waree

AU - Rinsurongkawong, Vadeerat

AU - Spelman, Amy

AU - Elamin, Yasir Y.

AU - Negrao, Marcelo V.

AU - Skoulidis, Ferdinandos

AU - Gay, Carl M.

AU - Cascone, Tina

AU - Gandhi, Saumil J.

AU - Lin, Steven H.

AU - Lee, Percy P.

AU - Carter, Brett W.

AU - Wu, Carol C.

AU - Antonoff, Mara B.

AU - Sepesi, Boris

AU - Lewis, Jeff

AU - Gibbons, Don L.

AU - Vaporciyan, Ara A.

AU - Le, Xiuning

AU - Jack Lee, J.

AU - Roy-Chowdhuri, Sinchita

AU - Routbort, Mark J.

AU - Gainor, Justin F.

AU - Heymach, John V.

AU - Lou, Yanyan

AU - Wu, Jia

AU - Zhang, Jianjun

AU - Vokes, Natalie I.

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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JF - Nature communications

IS - 1

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ER -

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

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