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

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 o...

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Detalles Bibliográficos
Autores principales: Hong, Lingzhi, Aminu, Muhammad, Li, Shenduo, Lu, Xuetao, Petranovic, Milena, Saad, Maliazurina B., Chen, Pingjun, Qin, Kang, Varghese, Susan, Rinsurongkawong, Waree, Rinsurongkawong, Vadeerat, Spelman, Amy, Elamin, Yasir Y., Negrao, Marcelo V., Skoulidis, Ferdinandos, Gay, Carl M., Cascone, Tina, Gandhi, Saumil J., Lin, Steven H., Lee, Percy P., Carter, Brett W., Wu, Carol C., Antonoff, Mara B., Sepesi, Boris, Lewis, Jeff, Gibbons, Don L., Vaporciyan, Ara A., Le, Xiuning, Jack Lee, J., Roy-Chowdhuri, Sinchita, Routbort, Mark J., Gainor, Justin F., Heymach, John V., Lou, Yanyan, Wu, Jia, Zhang, Jianjun, Vokes, Natalie I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9908867/
https://www.ncbi.nlm.nih.gov/pubmed/36755027
http://dx.doi.org/10.1038/s41467-023-36328-z
Descripción
Sumario: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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