Elisa DE Carlo1, Monica Schiappacassi2, Giacomo Pelizzari3, Tania Baresic4, Alessandro Del Conte5, Brigida Stanzione5, Valentina DA Ros5, Roberto Doliana2, Gustavo Baldassarre2, Alessandra Bearz5. 1. Clinical Oncology Department - Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy; elisa.decarlo@cro.it. 2. Molecular Oncology Department - Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy. 3. Oncology Department, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), Udine, Italy. 4. Nuclear Medicine Department - Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy. 5. Clinical Oncology Department - Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
Abstract
BACKGROUND: Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor approved for the treatment of T790M-positive non-small-cell lung cancer. More recently, osimertinib demonstrated improved disease control compared to other EGFR-TKIs. Multiple mechanisms of resistance have been described in T790M-positive patients who experienced treatment failure with osimertinib. CASE REPORT: We report the case of a 78-year-old non-smoker woman with stage IV EGFR L858R-positive lung adenocarcinoma presented with T790M mutation after five years of treatment with gefitinib. The patient was started on osimertinib, but after two and a half years of treatment experienced disease progression. The analyses of circulating tumor DNA using next-generation sequencing showed, together with the pre-existing T790M and exon 21 L858R, the presence of the EGFR C797G resistance mutation. CONCLUSION: Our case report revealed a rare EGFR-dependent acquired resistance mutation to osimertinib in circulating tumor DNA. Liquid biopsy appears to be a promising resource to understand the biology of osimertinib resistance by clonal evolution monitoring and the identification of novel resistance mechanisms.
BACKGROUND: Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor approved for the treatment of T790M-positive non-small-cell lung cancer. More recently, osimertinib demonstrated improved disease control compared to other EGFR-TKIs. Multiple mechanisms of resistance have been described in T790M-positive patients who experienced treatment failure with osimertinib. CASE REPORT: We report the case of a 78-year-old non-smoker woman with stage IV EGFR L858R-positive lung adenocarcinoma presented with T790M mutation after five years of treatment with gefitinib. The patient was started on osimertinib, but after two and a half years of treatment experienced disease progression. The analyses of circulating tumor DNA using next-generation sequencing showed, together with the pre-existing T790M and exon 21 L858R, the presence of the EGFR C797G resistance mutation. CONCLUSION: Our case report revealed a rare EGFR-dependent acquired resistance mutation to osimertinib in circulating tumor DNA. Liquid biopsy appears to be a promising resource to understand the biology of osimertinib resistance by clonal evolution monitoring and the identification of novel resistance mechanisms.
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