Small cell lung cancer transformation and the T790M mutation: A case report of two acquired mechanisms of TKI resistance detected in a tumor rebiopsy and plasma sample of EGFR-mutant lung adenocarcinoma

Greta Alì, Rossella Bruno, Mirella Giordano, Irene Prediletto, Letizia Marconi, Simonetta Zupo, Franco Fedeli, Alessandro Ribechini, Antonio Chella, Gabriella Fontanini

Research output: Contribution to journalArticlepeer-review

Abstract

The present study describes the case of a 45-year-old man diagnosed with metastatic lung adenocarcinoma, which harbored a deletion within exon 19 of the epidermal growth factor receptor (EGFR) gene. The patient was subsequently treated with gefitinib (250 mg/day orally from May 2013 to March 2014), but developed acquired resistance to the drug following 11 months of treatment. Tumor burden molecular analysis was performed on a tumor rebiopsy and plasma sample, and histological analysis was also performed on the tumor rebiopsy. A small cell transformation retaining the original EGFR mutation was detected in the tumor rebiopsy, while the T790M mutation together with the activating ex19del mutation were identified only in the plasma sample. The patient was treated with cytotoxic chemotherapy (off-label schedule with epirubicin 80 mg/mq and paclitaxel 160 mg/mq every 21 days for 6 cycles) and radiation (50.4 Gy administered in 28 fractions of 1.8 Gy once daily for 5.5 weeks) specific for small cell lung cancer, and may also have benefitted from treatment with a third generation T790M-specific EGFR-TKI. To better describe the mechanisms of resistance to TKI inhibitors and to optimize therapeutic regimens, the simultaneous analysis of tumor biopsies and circulating tumor DNA should be considered.

Original languageEnglish
Pages (from-to)4009-4012
Number of pages4
JournalOncology Letters
Volume12
Issue number5
DOIs
Publication statusPublished - Nov 1 2016

Keywords

  • Circulating free tumor DNA
  • Epidermal growth factor receptor T790M mutation
  • Epidermal growth factor receptor/tyrosine kinase inhibitor-acquired resistance
  • Lung adenocarcinoma
  • Small cell carcinoma transformation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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