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

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Feb 8

PMID 36755027

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

Affiliations

Soon will be listed here.

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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