Efficacy and Clinicogenomic Correlates of Response to Immune Checkpoint Inhibitors Alone or with Chemotherapy in Non-Small Cell Lung Cancer

Lingzhi Hong,Muhammad Aminu，Jianjun Zhang,Natalie I. Vokes

Nature communications（2023）SCI 1区

Cited 17|Views89

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.

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Key words

Cancer immunotherapy,Chemotherapy,Non-small-cell lung cancer,Science,Humanities and Social Sciences,multidisciplinary

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