Authors: 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
Published: 2023-02-08
DOI: 10.1038/s41467-023-36328-z
Source: Full article
AbstractThe 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), andSTK11andJAK2alterations as features associate with a higher likelihood of early progression on ICI-mono.CDKN2Aalterations 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.