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Clinical Perspectives to Overcome Acquired Resistance to Anti-Programmed Death-1 and Anti-Programmed Death Ligand-1 Therapy in Non-Small Cell Lung Cancer.

ABSTRACT: Immune checkpoint inhibitors have changed the paradigm of treatment options for non-small cell lung cancer (NSCLC). Monoclonal antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have gained wide attention for their application, which has been shown to result in prolonged survival. Nevertheless, only a limited subset of patients show partial or complete response to PD-1 therapy, and patients who show a response eventually develop resistance to immunotherapy. This article aims to provide an overview of the mechanisms of acquired resistance to anti-PD-1/PD-L1 therapy from the perspective of tumor cells and the surrounding microenvironment. In addition, we address the potential therapeutic targets and ongoing clinical trials, focusing mainly on NSCLC.

SUBMITTER: Lee YJ

PROVIDER: S-EPMC8175154 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Clinical Perspectives to Overcome Acquired Resistance to Anti-Programmed Death-1 and Anti-Programmed Death Ligand-1 Therapy in Non-Small Cell Lung Cancer.

Lee Yong Jun YJ Lee Jii Bum JB Ha Sang-Jun SJ Kim Hye Ryun HR

Molecules and cells 20210501 5

Immune checkpoint inhibitors have changed the paradigm of treatment options for non-small cell lung cancer (NSCLC). Monoclonal antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have gained wide attention for their application, which has been shown to result in prolonged survival. Nevertheless, only a limited subset of patients show partial or complete response to PD-1 therapy, and patients who show a response eventually develop resistance to immunotherapy. This ...[more]

PMID: 34001680

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Project description:BackgroundThe efficacy of anti-programmed cell death-1/ligand 1 antibody monotherapy (anti-PD-1/PD-L1 monotherapy) in patients with active brain metastases (BMs) is not established. Here, we aimed to evaluate the efficacy of anti-PD-1/PD-L1 monotherapy in non-small cell lung cancer (NSCLC) patients with active BMs.MethodsThis retrospective study included NSCLC patients treated with second-line or later-line anti-PD-1/PD-L1 monotherapy between December 2015 and August 2019. Patients were classified into those with or without active BMs, including symptomatic BMs requiring systemic steroids and untreated BMs. The progression-free survival (PFS) and overall survival (OS) of the patients with and without active BMs were compared. Intracranial and extracranial tumor responses were evaluated in patients with active BMs.ResultsWe analyzed 197 patients who had received anti-PD-1/PD-L1 monotherapy. Among them, 24 had active BMs. Among those without active BMs, 145 had no BMs and 28 had treated asymptomatic BMs. The PFS and OS of patients with active BMs were significantly shorter than those of patients without active BMs (1.3 vs. 2.7 months; P < 0.001, and 4.5 vs. 16.3 months; P = 0.001 respectively). For patients with active BMs, the intracranial and extracranial response rates were 13.3% and 26.7%, respectively. On multivariate analysis, active BMs, poor performance status (PS), and EGFR/ALK positivity were significant factors associated with shorter PFS. Active BMs and poor PS were significant factors associated with shorter OS.ConclusionsThis study suggested that anti-PD-1/PD-L1 monotherapy was not effective for NSCLC patients with active BMs. Further studies on immunotherapy are needed for patients with active BMs.Key pointsSignificant findings of the study: The present study showed that anti-PD-1/PD-L1 antibody monotherapy was not effective for non-small cell lung cancer patients with active brain metastases. Intracranial and extracranial response rates were 13.3% and 26.7%, respectively.What this study addsFurther studies on immunotherapy are needed for patients with active BMs.

Dataset Information

Clinical Perspectives to Overcome Acquired Resistance to Anti-Programmed Death-1 and Anti-Programmed Death Ligand-1 Therapy in Non-Small Cell Lung Cancer.

Publications

Clinical Perspectives to Overcome Acquired Resistance to Anti-Programmed Death-1 and Anti-Programmed Death Ligand-1 Therapy in Non-Small Cell Lung Cancer.

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