Cited by 106Lung Cancer Treatments and MutationsCancer Genomics and DiagnosticsHER2/EGFR in Cancer Research

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Primary resistance to osimertinib due to SCLC transformation: Issue of T790M determination on liquid re-biopsy

Minari, R., Bordi, P., Del Re, M., Facchinetti, F., Mazzoni, F., Barbieri, F., Camerini, A., Comin, C.E., Gnetti, L., Azzoni, C., Nizzoli, R., Bortesi, B., Rofi, E., Petreni, P., Campanini, N., Rossi, G., Danesi, R., Tiseo, M.·2018·Lung Cancer

DOI 10.1016/j.lungcan.2017.11.011

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Abstract

Objectives EGFR T790M mutation is the most common mechanism of resistance to first-/second-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) and could be overcome by third-generation EGFR-TKIs, such as osimertinib. Liquid biopsy, a non-invasive technique used to test the presence of the resistant mutation, may help avoiding tissue re-biopsy. However, analysing only circulating-free DNA, information about other less frequent and coexisting resistance mechanisms may remain unrevealed.Materials and methods All patients reported in this series participated in the ASTRIS trial, a real world treatment study testing the efficacy of osimertinib (80mg os die) in advanced T790M-positive NSCLC progressed to prior EGFR-TKI. Patients were considered eligible to osimertinib if T790M positive on tissue or plasma samples. In our patients, EGFR molecular testing on blood sample was conducted with digital droplet PCR (ddPCR).Results We report our experience of five patients treated with osimertinib after T790M detection on liquid biopsy that presented a disease progression at first tumor assessment mediated by SCLC transformation, as evidenced at tissue re-biopsies. All patients showed low ratio T790M/activating mutation in the blood before osimertinib (lower than 0.03). For three patients, EGFR mutational analysis was T790M-negative when re-assessed by using a less sensitive method (therascreen®) on the same liquid biopsy sample analysed by ddPCR before osimertinib therapy.Conclusion Although liquid biopsy is a relevant tool to diagnose T790M presence in NSCLC patients resistant to EGFR-TKI, in case of a low ratio T790M/activating mutation, tissue biopsy should be considered to exclude the presence of SCLC transformation and/or other concomitant resistance mechanisms.

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Authors: Minari, R., Bordi, P., Del Re, M., Facchinetti, F., Mazzoni, F., Barbieri, F., Camerini, A., Comin, C. E., Gnetti, L., Azzoni, C., Nizzoli, R., Bortesi, B., Rofi, E., Petreni, P., Campanini, N., Rossi, G., Danesi, R., & Tiseo, M.
Affiliations: University of Parma (IT)
Azienda Ospedaliero-Universitaria Careggi (IT)
Azienda Ospedaliero-Universitaria di Modena (IT)
Ospedale Versilia (IT)
University of Florence (IT)
Ospedale di Parma (IT)
University of Pisa (IT)
Azienda USL della Valle d’Aosta (IT)
Corresponding author: Tiseo, M.
ORCID: Minari, R.
Bordi, P.
Facchinetti, F.
Mazzoni, F.
Barbieri, F.
Camerini, A.
Gnetti, L.
Campanini, N.
Rossi, G.
Danesi, R.
Tiseo, M.
Venue: Lung Cancer
Publisher: Elsevier BV
Published: 2018-01
Volume: 115
Pages: 21-27
ISSN: 0169-5002 (ISSN-L)
DOI: 10.1016/j.lungcan.2017.11.011
OpenAlex: W2769241338
Cited by: 105
References: 25
Citations by year: 2026: 4 · 2025: 6 · 2024: 10 · 2023: 8 · 2022: 11 · 2021: 18 · 2020: 16 · 2019: 18 · 2018: 14
FWCI: 10.86
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Lung Cancer (publishedVersion)
PubMed (publishedVersion)
CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Keywords: osimertinib, T790M mutation, small cell lung cancer transformation, liquid biopsy, circulating tumor DNA, EGFR tyrosine kinase inhibitors, treatment resistance, droplet digital PCR, non-small cell lung cancer
MeSH terms: Acrylamides, Aged, Aniline Compounds, Antineoplastic Agents, Biopsy, Carcinoma, Non-Small-Cell Lung, Cell Transformation, Neoplastic, DNA Mutational Analysis, Female, Humans, Indoles, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Staging, Piperazines, Pyrimidines, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, ErbB Receptors

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Primary resistance to osimertinib due to SCLC transformation: Issue of T790M determination on liquid re-biopsy

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