Rebiopsy Feasibility and Clinical Impact on Metastatic Non-Small-Cell Lung Cancer With EGFR/ALK/ROS Oncogenic Driver Progression After Optimal Targeted Therapy: A Multicenter Real-World Analysis

Clin Lung Cancer. 2025 Dec;26(8):e724-e730. doi: 10.1016/j.cllc.2025.08.009. Epub 2025 Aug 21.

Abstract

Background: For metastatic non-small-cell lung cancer (mNSCLC) patients with oncogenic driver progression after tyrosine kinase inhibitors (TKIs), obtaining a new mutational profile is recommended to assess the mechanism of resistance. The feasibility of that recommendation and its clinical impact remain poorly studied.

Methods: mNSCLC patients with EGFR mutation and ALK or ROS translocation progressing on optimal TKI therapy were screened for inclusion in an immunochemotherapy trial not requiring a new molecular profile determination. This analysis evaluated the rebiopsy rate and its clinical impact.

Results: Among 148 patients, 79 (53.4%) analyzable re-biopsies showed 72/132 (54.6%) with EGFR mutations, 7/13 (53.8%) had ALK translocations and no (0/5) ROS translocations. Seventy-nine re-biopsies were tissue (37, 46.8%), liquid (26, 32.9%) or both samples (16, 20.3%). For patients harboring EGFR mutations, the rebiopsy was not contributive for 12/72 (16.7%), the initial mutation was not found for 9/72 (12.5%) and only the unchanged initial profile was detected for 22/72 (30.6%); new information was provided for 29/72 (40.3%). Among patients with ALK-translocated mNSCLCs, re-biopsies enabled identification of resistance mechanisms for 20%. Overall survival did not differ between patients with rebiopsy and those without.

Conclusions: In this population of patients with oncogenic driver progression under optimal targeted TKIs and in sufficiently good general condition to be included in an immunochemotherapy trial, only half were re-biopsied. Rebiopsy does not seem to improve the outcomes of these patients.

Keywords: Biopsy; Chemotherapy; Management; Outcomes; Target therapy.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase / genetics
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics
  • ErbB Receptors / genetics
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Mutation
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics

Substances

  • ErbB Receptors
  • EGFR protein, human
  • Anaplastic Lymphoma Kinase
  • ALK protein, human
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • ROS1 protein, human
  • Protein-Tyrosine Kinases