依维莫司
神经内分泌癌
门1
PTEN公司
肿瘤科
神经内分泌肿瘤
医学
癌
内科学
内分泌系统
PI3K/AKT/mTOR通路
化学
生物化学
细胞凋亡
激素
作者
Alice Boilève,Matthieu Faron,Sarah Fodil-Cherif,Arnaud Bayle,Livia Lamartina,David Planchard,Lambros Tselikas,Christina Kanaan,Jean Yves Scoazec,Michel Ducreux,Antoîne Italiano,Éric Baudin,Julien Hadoux
标识
DOI:10.1016/j.ejca.2023.03.024
摘要
Key molecular alterations (MA) of neuroendocrine neoplasm (NEN) of various grade/primaries have been described but the applicability of molecular profiling (MP) for precision medicine in NEN remains to be demonstrated.We conducted a retrospective study of all patients with metastatic NEN who had MP on tumour tissue at Gustave Roussy. The primary objective was to assess the clinical applicability of MP by evaluating the growth modulator index (GMI) as the primary end-point.MPs were obtained in 114 out of 156 eligible patients, including 12% NET-G1, 42% NET-G2, 13% NET-G3 and 35% neuroendocrine carcinoma (NEC). Primary sites were lung/thymus (40%), pancreas (19%), gastro-intestinal (16%), head&neck (10%), unknown (10%) and others (10%) with synchronous metastases in 61% of the patients. Most frequent MA were: MEN1 (25%), PTEN (13%), TP53 (11%) and TSC2 (9%), in neuroendocrine tumour (NET), and TP53 (50%) and RB1 (18%) in NEC. ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) classification of these MA were: I(5%), III(20%), IV(23%), X(27%); a putative actionable MA was identified in 48% patients. Median TMB was 5.7 Mut/Mb, with 3 TMB > 10 and 1 MSI NET. No MA was found in 26% patients. Molecularly matched treatment was administered to 19 patients (4 NEC, 15 NET): immunotherapy (n = 3), tipifarnib (n = 1), NOTCHi (n = 1), EGFRi (n = 2), HER2i (n = 1) and everolimus (n = 11). Overall, 67% of patients had a clinical benefit defined as a GMI over 1.3 with a 78% disease control rate.We report 48% of NEN with a putative actionable MA of which 35% received molecularly matched treatment, with a clinical benefit in 67% of the cases.
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