osimertinib and Carcinoma--Neuroendocrine

Topics: Acrylamides; Aniline Compounds; Carcinoma, Neuroendocrine; Carcinoma, Non-Small-Cell Lung; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors

Topics: Acrylamides; Adenocarcinoma of Lung; Aged; Aniline Compounds; Antineoplastic Agents; Carcinoma, Neuroendocrine; Drug Resistance, Neoplasm; ErbB Receptors; Female; Gene Fusion; Humans; Lung Neoplasms; Protein Kinase Inhibitors; Receptor, Notch2; Receptor, trkA

Epidermal growth factor receptor (EGFR) exon 20 insertions comprise 4-10 % of EGFR mutations in non-small cell lung cancer (NSCLC) and are associated with primary resistance to first and second generation EGFR tyrosine kinase inhibitors (TKIs). In vitro and preclinical animal studies have shown that osimertinib exerts antitumor activity against EGFR exon 20 mutation positive NSCLC. We report on a cohort of advanced stage NSCLC patients who harbor an EGFR exon 20 mutation and received osimertinib treatment.. Twenty-one patients were treated with osimertinib 80 or 160 mg once daily from April 2016 to June 2018, in four institutions in the Netherlands. Data were obtained retrospectively. Progression free survival (PFS), disease control rate (DCR), overall survival (OS) and objective response rate (ORR) were assessed using RECIST v1.1.. Thirteen patients received prior platinum-based chemotherapy, and three patients a first - or second generation EGFR TKI. We observed 1 partial response, 17 patients with stable disease and 3 with progressive disease as best response to osimertinib (ORR 5 %). Median PFS was 3.6 (95 % CI, 2.6-4.5) months. PFS did not differ for patients with co-occurring TP53 mutations (p = 0.937). The DCR at three months was 71 %. Median OS was 8.7 (95 % CI, 1.1-16.4) months.. Osimertinib has limited antitumor activity in patients with EGFR exon 20 mutated NSCLC, with an ORR of 5 %.

Topics: Acrylamides; Adenocarcinoma of Lung; Adult; Aged; Aged, 80 and over; Aniline Compounds; Carcinoma, Large Cell; Carcinoma, Neuroendocrine; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Exons; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Prognosis; Protein Kinase Inhibitors; Retrospective Studies; Survival Rate

Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is selective for both epidermal growth factor receptor tyrosine kinase inhibitor-sensitizing and T790M resistance mutations. Almost all patients who initially respond to an epidermal growth factor receptor tyrosine kinase inhibitor subsequently report disease progression. Epidermal growth factor receptor-dependent resistance mechanisms, bypass pathway activation, and histological transformation have been reported with osimertinib therapy.. We report a case of a 64-year-old Asian man with epidermal growth factor receptor T790M-positive adenocarcinoma that transformed to epidermal growth factor receptor T790M-negative large-cell neuroendocrine carcinoma after osimertinib therapy. A prompt rebiopsy revealed a rare mechanism of resistance to epidermal growth factor receptor tyrosine kinase inhibitor, and subsequently treatment with carboplatin and etoposide was effective.. Despite the promising emergence of circulating tumoral DNA testing, this case report emphasizes the importance of rebiopsy of a progressive epidermal growth factor receptor-mutant tumor.

Topics: Acrylamides; Adenocarcinoma of Lung; Aniline Compounds; Carcinoma, Neuroendocrine; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Protein Kinase Inhibitors

Acquired resistances to tyrosine kinase inhibitors in non-small cell lung cancer develop after 9 - 12 month. In 60 % of the cases these resistances arise because of a secondary EGFR-T790 M resistance mutation. This report is describing the case of a patient who developed parallel two different mechanisms of resistance: A T790 M resistance mutation and a transformation into a small cell neuroendocrine cancer. Under therapy with Osimertinib and chemotherapy with carboplatin and etoposide the tumor responsed partially.. Erworbene Resistenzen gegenüber Tyrosinkinaseinhibitoren beim nicht kleinzelligen Lungenkarzinom entwickeln sich nach etwa 9 – 12 Monaten. In etwa 60 % der Fälle entstehen diese durch eine sekundäre EGFR-T790 M Resistenzmutation. In dieser Kasuistik wird der Fall einer Patientin mit einer Mutation im EGFR Exon 19 beschrieben. Es entwickeln sich unter TKI-Therapie 2 parallele Resistenzmechanismen. Zum einen eine T790M-Resistenzmutation, zum anderen die Transformation in ein kleinzelliges neuroendokrines Karzinom. Unter der Therapie mit Osimertinib sowie paralleler Chemotherapie mit Carboplatin und Etoposid konnte nach 2 Zyklen eine partielle Remission erzielt werden.

Topics: Acrylamides; Aniline Compounds; Antineoplastic Agents; Carboplatin; Carcinoma, Neuroendocrine; Carcinoma, Non-Small-Cell Lung; Disease Progression; Drug Resistance, Neoplasm; ErbB Receptors; Etoposide; Humans; Lung Neoplasms; Mutation; Piperazines; Protein Kinase Inhibitors; Treatment Outcome