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PD-(L)1 Inhibitor Monotherapy vs Chemoimmunotherapy for Advanced NSCLC With High PD-L1 Expression: A Systematic

Alessandro Di Federico1,2, Samuele Compagno1,2, Francesco Mantuano1,2

  • 1Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

JAMA Oncology
|June 4, 2026
PubMed
Summary

Chemoimmunotherapy significantly improves overall survival and progression-free survival compared to programmed cell death 1 (PD-1) or PD-1 ligand 1 (PD-L1) inhibitor monotherapy in advanced non-small cell lung cancer (NSCLC) patients with high PD-L1 expression.

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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells

Published on: February 8, 2018

Area of Science:

  • Oncology
  • Immunotherapy
  • Clinical Trials

Background:

  • Advanced non-small cell lung cancer (NSCLC) with high programmed cell death 1 ligand 1 (PD-L1) expression is often treated with PD-1/PD-L1 inhibitor monotherapy.
  • The benefit of adding chemotherapy to PD-1/PD-L1 inhibitor monotherapy in this patient population remains unclear.

Purpose of the Study:

  • To compare overall survival (OS) and progression-free survival (PFS) between PD-(L)1 inhibitor monotherapy and chemoimmunotherapy in treatment-naive patients with advanced NSCLC and high PD-L1 expression.

Main Methods:

  • A systematic search of PubMed, Embase, and conference proceedings identified phase 3 randomized clinical trials (RCTs) published before August 3, 2025.
  • Data extraction and synthesis included meta-regression, network meta-analysis, and reconstructed individual patient data from Kaplan-Meier curves to compare OS and PFS.

Main Results:

  • Chemoimmunotherapy demonstrated significantly improved OS (HR, 0.63) and PFS (HR, 0.44) compared to chemotherapy alone.
  • Both chemoimmunotherapy and PD-(L)1 inhibitor monotherapy improved survival compared to chemotherapy.
  • Chemoimmunotherapy showed superior OS (HR, 0.85) and PFS (HR, 0.61) compared to PD-(L)1 inhibitor monotherapy, supported by individual patient data analysis.

Conclusions:

  • Chemoimmunotherapy offers significant survival benefits over PD-(L)1 inhibitor monotherapy for advanced NSCLC patients with high PD-L1 expression.
  • These findings suggest chemoimmunotherapy as a preferred first-line treatment option for this patient group.
  • Prospective trials are warranted to validate these meta-analysis results.