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Updated: Sep 11, 2025

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer

Published on: September 8, 2023

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First-line immunotherapy in advanced non-squamous non-small cell lung cancer patients with rare mutations: a

Wenli Cao1, Furong Kou1, Weiheng Hu2

  • 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Comprehensive Clinical Trial Ward, Peking University Cancer Hospital & Institute, Beijing, China.

Translational Lung Cancer Research
|August 13, 2025
PubMed
Abstract

Insights

First-line immunotherapy shows promise for advanced non-small cell lung cancer (NSCLC) patients with rare mutations. These patients may benefit from immunotherapy, demonstrating comparable outcomes to mutation-negative groups and superior overall survival compared to targeted therapy.

Area of Science:

  • Oncology
  • Genetics
  • Immunotherapy

Background:

  • Immunotherapy is standard for advanced non-small cell lung cancer (NSCLC).
  • Efficacy of immunotherapy in NSCLC patients with rare mutations is not well-established.
  • Rare mutations include HER2, MET, BRAF, and NTRK.

Purpose of the Study:

  • To evaluate the efficacy of first-line immunotherapy in advanced NSCLC patients with rare mutations.
  • To compare immunotherapy outcomes in rare mutation NSCLC patients versus mutation-negative NSCLC patients.
  • To compare first-line immunotherapy versus targeted therapy in rare mutation NSCLC patients.

Main Methods:

  • Retrospective study of 2,107 advanced non-squamous NSCLC patients.
  • Inclusion of patients with rare mutations (HER2, MET, BRAF, NTRK) and mutation-negative controls.
  • Comparison of progression-free survival (PFS) and overall survival (OS) using log-rank test.

Main Results:

  • No significant difference in PFS or OS between rare mutation and mutation-negative groups receiving first-line immunotherapy.
  • Rare mutation patients receiving first-line immunotherapy had superior median OS compared to targeted therapy (34.40 vs. 16.37 months, P=0.008).
  • No significant difference in median PFS between immunotherapy and targeted therapy for rare mutation patients (14.53 vs. 7.03 months, P=0.10).

Conclusions:

  • First-line immunotherapy may benefit advanced non-squamous NSCLC patients with rare mutations.
  • Immunotherapy offers improved overall survival for rare mutation NSCLC compared to targeted therapy.
  • Further research is warranted to optimize treatment strategies for NSCLC with rare mutations.
Keywords:
Non-small cell lung cancer (NSCLC)immunotherapyrare mutations

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