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Small cell lung cancer differentiation in patients with driver mutant non-small cell lung cancer: a single center

Oğuzhan Yıldız1, Melek Karakurt Eryılmaz2, Ali Fuat Gürbüz2

  • 1Department of Medical Oncology, Necmettin Erbakan University School of Medicine , Akyokuş, Konya, 42080, Turkey. dr.oguzhan@outlook.com.

Journal of Cancer Research and Clinical Oncology
|July 2, 2025
PubMed
Abstract

Insights

Small cell lung cancer (SCLC) differentiation occurred in 13.6% of metastatic non-small cell lung cancer (mNSCLC) patients with driver mutations treated with tyrosine kinase inhibitors (TKIs). This highlights the need for careful monitoring during TKI therapy for potential SCLC transformation.

Area of Science:

  • Oncology
  • Thoracic Oncology
  • Molecular Oncology

Background:

  • Metastatic non-small cell lung cancer (mNSCLC) treatment often involves targeted therapies like tyrosine kinase inhibitors (TKIs) for patients with driver mutations.
  • Progression under TKI therapy in driver-mutant mNSCLC raises concerns about the potential development of small cell lung cancer (SCLC) differentiation, an aggressive subtype.
  • SCLC differentiation is associated with poorer prognoses, necessitating understanding its occurrence in TKI-treated mNSCLC patients.

Purpose of the Study:

  • To investigate the incidence of SCLC differentiation in driver-mutant mNSCLC patients who have undergone at least one line of TKI therapy.
  • To present single-center data on SCLC transformation rates in this specific patient population.

Main Methods:

  • Retrospective review of medical records for 144 patients with driver-mutant mNSCLC treated with at least one TKI.
  • Analysis included patient demographics, driver mutation status (EGFR, ALK, ROS1), TKI treatment lines, and incidence of SCLC differentiation confirmed by biopsy post-progression.
  • Data collected from Necmettin Erbakan University Faculty of Medicine Hospital between April 2013 and January 2024.

Main Results:

  • Out of 144 patients, 122 had EGFR mutations, 21 had ALK mutations, and 1 had a ROS1 mutation.
  • SCLC differentiation was observed in 3 out of 22 patients (13.6%) who underwent biopsy after disease progression, all with EGFR mutations.
  • Two patients developed SCLC differentiation after first-line TKI therapy, and one developed it after second-line TKI therapy.

Conclusions:

  • The observed rate of SCLC differentiation (13.6%) in this cohort of driver-mutant mNSCLC patients treated with TKIs is higher than the generally reported rare incidence (1-3%).
  • Findings suggest SCLC differentiation is a potential event in mNSCLC patients receiving TKI therapy, emphasizing the need for vigilance.
  • Careful monitoring and early detection of SCLC differentiation are crucial during the follow-up of these patients.
Keywords:
Metastatic non-small cell lung cancerSmall cell lung cancer differentiationTyrosine kinase inhibitors

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