# Pretreatment clinical and hematological predictors of efficacy and immune-related adverse events in patients with advanced non-small cell lung cancer receiving first-line chemotherapy combined with immune checkpoint inhibitors

**Authors:** Shun Matsuura, Kensuke Kita, Kyohei Matsushita, Takumi Nagasaki, Ryo Suzuki, Yuya Yamamoto, Kotaro Yamada, Ryuuichi Nakamura, Norimichi Akiyama, Kazuki Tanaka, Naoki Koshimizu

PMC · DOI: 10.1186/s12885-026-15733-9 · 2026-02-12

## TL;DR

This study identifies pretreatment factors that predict treatment response and side effects in lung cancer patients receiving immune therapy plus chemotherapy.

## Contribution

The study identifies novel clinical and hematological predictors for treatment efficacy and immune-related adverse events in NSCLC patients.

## Key findings

- ECOG-PS, metastases count, and biomarker levels predict progression-free survival.
- ECOG-PS, metastases count, and neutrophil-to-lymphocyte ratio predict overall survival.
- Patients without liver metastases have higher rates of immune-related adverse events.

## Abstract

The combination of immune checkpoint inhibitors (ICI) and platinum-based chemotherapy has rapidly become the standard first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC). However, identifying reliable predictive factors of treatment response remains a significant clinical challenge. This study comprehensively analyzed pretreatment predictive factors in patients with advanced lung cancer who received first-line ICI–chemotherapy combination therapy.

We retrospectively analyzed clinical data from 100 patients with advanced NSCLC who received first-line ICI–chemotherapy. Univariate and multivariate Cox proportional hazards regression analyses were used to identify prognostic factors for progression-free survival (PFS) and overall survival (OS). Univariate logistic regression analysis was used to identify factors affecting the incidence of immune-related adverse events (irAEs).

Multivariate analysis for PFS identified Eastern Cooperative Oncology Group performance status (ECOG-PS), number of metastases, lactate dehydrogenase level, cytokeratin 19 fragment antigen level, and programmed death-ligand 1 expression as independent predictors of PFS. Multivariate analysis for OS identified ECOG-PS, number of metastases, and neutrophil-to-lymphocyte ratio as significant independent predictors of OS. Patients with liver metastases showed a significantly lower incidence of irAEs than patients without liver metastases (8.3% vs. 29.7%, P = 0.013). The occurrence of irAEs was associated with longer PFS and OS.

This study identified pretreatment clinical and hematological factors that could predict the efficacy of ICI–chemotherapy. Furthermore, the absence of liver metastases was associated with a higher incidence of irAEs. These results underscore the critical need for individualized treatments and potential adjustment of strategies for high-risk groups to achieve a long-term durable response and better survival.

The online version contains supplementary material available at 10.1186/s12885-026-15733-9.

## Linked entities

- **Diseases:** non-small cell lung cancer (MONDO:0005233)

## Full-text entities

- **Diseases:** non-small cell lung cancer (MESH:D002289)
- **Chemicals:** immune (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13014870/full.md

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Source: https://tomesphere.com/paper/PMC13014870