Osimertinib plus Selumetinib in EGFR-Mutated Non–Small Cell Lung Cancer After Progression on EGFR-TKIs: A Phase Ib, Open-Label, Multicenter Trial (TATTON Part B)

医学 奥西默替尼 塞鲁美替尼 T790米 内科学 肿瘤科 耐受性 不利影响 吉非替尼 胃肠病学 癌症 埃罗替尼 表皮生长因子受体 克拉斯 结直肠癌
作者
James Chih‐Hsin Yang,Yuichiro Ohe,Chao‐Hua Chiu,Xiaoling Ou,Mireille Cantarini,Pasi A. Jänne,Ryan J. Hartmaier,Myung‐Ju Ahn
出处
期刊:Clinical Cancer Research [American Association for Cancer Research]
卷期号:28 (19): 4222-4231 被引量:9
标识
DOI:10.1158/1078-0432.ccr-21-4329
摘要

MEK/ERK inhibition can overcome acquired resistance to osimertinib in preclinical models. Osimertinib (epidermal growth factor receptor [EGFR]-tyrosine kinase inhibitor [TKI]) plus selumetinib (mitogen-activated protein kinase [MEK]1/2 inhibitor) was assessed in the global TATTON study.This multicenter, open-label, Phase 1b study expansion cohort enrolled patients (aged {greater than or equal to}18 years) with advanced MET-negative, EGFRm NSCLC who had progressed on EGFR-TKIs. Patients were assigned to one of two cohorts by prior first-/second-generation [1G/2G] or T790M-directed EGFR-TKI and received osimertinib 80 mg QD and intermittent selumetinib 75 mg BID PO. Safety and tolerability (primary objective) and antitumor activity determined by objective response rate (ORR), and progression-free survival (PFS) using RECIST version 1.1 were assessed. Data cutoff: March 4, 2020.Forty-seven patients received treatment (prior 1G/2G EGFR-TKI, n=12; prior 3G EGFR-TKI, n=35). Forty-four (94%) patients were Asian; 30 (64%) had baseline exon 19 deletion. Most common AEs were diarrhea (89%), decreased appetite (40%), and stomatitis (32%); 11/47 patients (23%) had an AE Grade {greater than or equal to}3 possibly causally selumetinib-related. ORR was 66.7% (95% confidence interval: 34.9-90.1) in the prior 1G/2G EGFR-TKI group, 22.9% (10.4-40.1) in the prior 3G EGFR-TKI group, and 34.0% (2.7-7.2) overall; median PFS was 15.0 (2.7-33.0), 2.8 (1.6-5.5), and 4.2 months (2.7-7.2), respectively.In this small study, AEs and tolerability of osimertinib plus selumetinib were as expected, based on previous studies. The combination demonstrated antitumor activity supportive of further investigation in patients with MET-negative, EGFRm advanced NSCLC, who had progressed on a previous EGFR-TKI.
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