Primary resistance to osimertinib due to SCLC transformation: Issue of T790M determination on liquid re-biopsy
| Autor: | Camilla E. Comin, Francesca Mazzoni, Rita Nizzoli, Cinzia Azzoni, Letizia Gnetti, Eleonora Rofi, Romano Danesi, Paola Bordi, Paolo Petreni, Beatrice Bortesi, Roberta Minari, Giulio Rossi, Fausto Barbieri, Andrea Camerini, Marcello Tiseo, Francesco Facchinetti, M. Del Re, Nicoletta Campanini |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Pulmonary and Respiratory Medicine Male medicine.medical_specialty Cancer Research Lung Neoplasms EGFR Biopsy DNA Mutational Analysis ddPCR Antineoplastic Agents NSCLC T790M Piperazines 03 medical and health sciences 0302 clinical medicine Internal medicine Carcinoma Non-Small-Cell Lung medicine Humans Osimertinib Liquid biopsy Protein Kinase Inhibitors Aged Neoplasm Staging SCLC transformation Acrylamides Aniline Compounds business.industry Disease progression Middle Aged Activating mutation respiratory tract diseases Mutational analysis ErbB Receptors 030104 developmental biology Cell Transformation Neoplastic Drug Resistance Neoplasm 030220 oncology & carcinogenesis Concomitant Re biopsy Mutation Female business |
| Zdroj: | Lung cancer (Amsterdam, Netherlands). 115 |
| ISSN: | 1872-8332 |
| Popis: | 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 (80 mg 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. |
| Databáze: | OpenAIRE |
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