Histo-Molecular Factors of Response to Combined Chemotherapy and Immunotherapy in Non-Small Cell Lung Cancers

Sep 24, 2026

Uploaded by Franzy

Chemo-immunotherapy (CIT) is standard care for advanced non-small cell lung cancer (NSCLC), yet the real-world value of routinely available histo-molecular biomarkers for predicting CIT efficacy remains insufficiently defined. This multicenter study evaluates CIT activity in relation to oncogenic drivers, focusing on STK11 and TP53 mutations and MET overexpression. Progression-free survival served as the primary endpoint, with overall survival and objective response rate as secondary endpoints.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Background and Rationale

Biomarkers for immunotherapy response

Driver alterations and immune response

Methods and Endpoints

Results

Conclusion

Introduction

Targeted Oncology (2023) 18:927–939 [https://doi.org/10.1007/s1](https://doi.org/10.1007/s1) 1523-023-01009-w Histo‑Molecular Factors of Response to Combined Chemotherapy and Immunotherapy in Non‑Small Cell Lung Cancers Marine Marchal1 · Vincent Leroy2 · Hélène Behal3 · Eric Dansin4 · Nicolas Paris5 · Soraya Bordier6 · Sarah Humez7,8 · Fabienne Escande9 · Clément Gauvain1 · Alexis B. Cortot1,8 Accepted: 11 October 2023 / Published online: 3 November 2023 © The Author(s) 2023 Abstract Background Chemo-immunotherapy (CIT) is the standard of care for advanced non-small cell lung cancer (NSCLC), but the impact of routinely available histo-molecular biomarkers on its efficacy has not yet been fully assessed. Objective The purpose of this multicenter study was to evaluate the clinical activity of CIT according to oncogenic drivers, STK11 and TP53 mutations, and MET overexpression. Patients and methods Patients receiving CIT for advanced NSCLC with available comprehensive molecular profile were included. The primary endpoint was progression-free survival (PFS), adjusted on main confounding factors, and secondary endpoints were overall survival (OS) and objective response rate. Results Among the 195 patients included between September 2018 and October 2021, 88 (41%) had a KRAS mutation, 16 (8.2%) an EGFR mutation or an ALK, ROS1, or RET rearrangement, 11 (5.6%) a BRAF mutation, 6 (3.1%) a MET exon 14 mutation or MET amplification, and 5 (2.6%) a HER2 mutation. Seventy-seven patients (39.5%) had none of these alterations. The median PFS was 6.4 months (95% CI 5.3–7.3) . Per subgroup, the median PFS was 7.1 months (5.4–8.9) for KRAS, 5.5 months (2 .5–15.3) for EGFR/ALK/ROS1/RET, 12.9 months (2 .6–not reached [NR]) for BRAF, 1.5 months (0 .6–NR) for MET, 3.9 months (2.6–NR) for HER2, and 5.6 months (4.7–7.8) for patients without any oncogenic alteration. No difference in PFS was observed between the KRAS, BRAF, EGFR/ALK/ROS1/RET, and no-driver subgroups. STK11 mutations were associated with poor PFS (HR 1.59 [95% CI 1.01–2.51]) whereas TP53 mutations had no impact. MET overexpression was associated with longer PFS (HR 0.59 [95% CI 0.35–0.99]) . Conclusion This study suggests that the efficacy of combining pembrolizumab with pemetrexed and platinum-based chemotherapy differs according to the histo-molecular biomarkers, which may help to identify patients liable to benefit from CIT. Extended author information available on the last page of the article 1 Introduction Over the past 15 years, treatment of advanced non-small cell lung cancer (NSCLC) has undergone profound changes, with the development of targeted therapies and immune checkpoint inhibitors (ICIs). These therapeutics offer the possibility of long-term disease control. Meanwhile, histo-molecular profiling has become part of routine care, its aim being to detect targetable oncogenic alterations and biomarkers predictive of response to both targeted therapies and immunotherapy [1] . Inhibitors of programmed cell death-1 (PD1) or programmed cell death ligand-1 (PDL1) have significantly improved the prognosis of patients with advanced NSCLC, but their efficacy is in fact variable, and only a subset of patients actually derives a prolonged benefit from immunotherapy [2, 3] . Several potential biomarkers, reflecting the balance between the pro-inflammatory anti-tumor immune response and immune evasion mechanisms, may allow more accurate prediction of the clinical response to immunotherapy, but only the PDL1 tumor proportion score (TPS) is currently used in clinical practice [4] . Testing for a driver oncogene alteration may help determine which patients may benefit from ICI treatment as monotherapy. Anti-PD(L)1 agents are associated with poor outcomes in patients with EGFR mutations and ALK rearrangements [5–8] . This lack of sensitivity may be related to an uninflamed tumor micro-environment and a low tumor mutational burden (TMB) [9, 10] . As a conse

FAQs

What is the main purpose of this multicenter study?

To evaluate the clinical activity of chemo-immunotherapy in advanced NSCLC according to oncogenic drivers, specifically STK11 and TP53 mutations and MET overexpression.

How was treatment response assessed in the study?

Progression-free survival (PFS) adjusted for main confounders was the primary endpoint, with overall survival (OS) and objective response rate as secondary endpoints.

Which biomarkers were associated with PFS outcomes?

STK11 mutations were associated with poor PFS, while MET overexpression was associated with longer PFS; TP53 mutations showed no impact.

Sep 24, 2026

Uploaded by Franzy