Small-Cell Lung Cancer Transformation as a Mechanism of Resistance to Pralsetinib in RET-Rearranged Lung Adenocarcinoma: A Case Report.

Clin Lung Cancer

Department of Medical Oncology, Centre Léon Bérard, Lyon, France; Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1052, CNRS UMR5286, Centre Léon Bérard, Cancer Research Center of Lyon, Lyon, France. Electronic address:

Published: January 2023

AI Article Synopsis

  • Resistance to RET-specific tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) mainly arises from mechanisms not involving RET itself.
  • A unique case involving a patient with RET-rearranged lung adenocarcinoma (LUAD) evolving into small-cell lung cancer (SCLC) after 14 months of treatment with pralsetinib showcases this resistance mechanism.
  • The case highlights the importance of rebiopsy in patients experiencing treatment failure, as histological changes may necessitate adjustments in therapy to effectively manage the disease.

Article Abstract

The majority of resistance to Rearranged during transfection (RET)-specific tyrosine kinase inhibitors (TKI) described in RET-rearranged non-small cell lung cancer (NSCLC) patients are driven by RET-independent mechanisms. We provide the first case report of a RET-rearranged lung adenocarcinoma (LUAD) transformation into small-cell lung cancer (SCLC) as a mechanism of acquired resistance to pralsetinib. A 43-year-old patient presented with a RET-rearranged LUAD revealed by pleural effusion. After 14 months of response to pralsetinib, biopsy of a progressive pleural lesion found a phenotypic transformation into SCLC. Molecular analysis identified the same RET fusion and TP53 mutation in both primary adenocarcinoma and recurrence as SCLC. The patient achieved partial response after switch to carboplatin and etoposide chemotherapy and presented with progression disease after 6 months. Histological transformation could be a mechanism of resistance to RET-TKIs and rebiopsy should be considered to adapt subsequent treatment.

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Source
http://dx.doi.org/10.1016/j.cllc.2022.10.005DOI Listing

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