title: Osimertinib (AZD9291) and CNS Response in Two Radiotherapy-Naïve Patients with EGFR-Mutant and T790M-Positive Advanced Non-Small Cell Lung Cancer.
abstract: The discovery of sensitizing epidermal growth factor receptor (EGFR) mutations as a predictive marker of sensitivity to first-generation EGFR tyrosine kinase inhibitors (TKIs) has dramatically changed the paradigm of care for advanced non-small cell lung cancer (NSCLC) patients. Unfortunately, the majority of patients with EGFR-mutant NSCLC treated with EGFR-TKIs develop acquired resistance within 14-16 months. T790M mutation recently emerged as a major determinant of acquired resistance to gefitinib and erlotinib. Osimertinib (AZD9291) is a novel mono-anilino-pyrimidine third-generation EGFR TKI targeting both sensitizing and T790M EGFR-mutation which showed promising results in T790M-positive NSCLC. Here we report two cases of gefitinib- or erlotinib-pretreated NSCLCs with a T790M mutation-positive (as assessed on plasma through the therascreen EGFR test) disease and untreated, asymptomatic central nervous system metastases that responded to treatment with osimertinib.
authors.affiliation: Department of Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori 1, 06156, Perugia, Italy. biagio.ricciuti@gmail.com.
authors.forename: Biagio
authors.initials: B
authors.lastname: Ricciuti
authors.affiliation: Department of Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori 1, 06156, Perugia, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Chiari
authors.affiliation: Department of Neuroradiology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Chiarini
authors.affiliation: Department of Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori 1, 06156, Perugia, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
authors.affiliation: Department of Diagnostic Imaging, University of Perugia, Perugia, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Maiettini
authors.affiliation: Department of Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori 1, 06156, Perugia, Italy.
authors.forename: Vienna
authors.initials: V
authors.lastname: Ludovini
authors.affiliation: Department of Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori 1, 06156, Perugia, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Metro
mesh_terms: D000178:Acrylamides; D000368:Aged; D000814:Aniline Compounds; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000517:prevention & control; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D007211:Indoles; D011743:Pyrimidines
chemical_list: D000178:Acrylamides; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D010879:Piperazines; D047428:Protein Kinase Inhibitors; C000596361:osimertinib; D007211:Indoles; D011743:Pyrimidines; C512478:EGFR protein, human