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)

James Chih Hsin Yang, Yuichiro Ohe, Chao Hua Chiu, Xiaoling Ou, Mireille Cantarini, Pasi A. Jänne, Ryan J. Hartmaier, Myung Ju Ahn

研究成果: 雜誌貢獻文章同行評審

10 引文 斯高帕斯(Scopus)

摘要

Purpose: MEK/ERK inhibition can overcome acquired resistance to osimertinib in preclinical models. Osimertinib [EGFR- tyrosine kinase inhibitor (TKI)] plus selumetinib (MEK1/2 inhibitor) was assessed in the global TATTON study. Patients and Methods: This multicenter, open-label, phase Ib study expansion cohort enrolled patients (aged ≥18 years) with MET-negative, EGFRm advanced NSCLC who had progressed on EGFR-TKIs. Patients were assigned to one of two cohorts by prior first- or second-generation or T790M-directed EGFR-TKI and received osimertinib 80 mg every day and intermittent selumetinib 75 mg twice a day orally. Safety and tolerability (primary objective) and antitumor activity determined by objective response rate (ORR), and progression-free survival (PFS) using RECIST v1.1 were assessed. Data cutoff: March 4, 2020. Results: Forty-seven patients received treatment (prior first- or second-generation EGFR-TKI, n = 12; prior T790M-directed 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 ≥3 possibly causally selumetinib-related. ORR was 66.7% [95% confidence interval (CI), 34.9-90.1] in the prior first- or second-generation EGFR-TKI group, 22.9% (95% CI, 10.4-40.1) in the prior T790M-directed EGFR-TKI group, and 34.0% (95% CI, 20.9-49.3) overall; median PFS was 15.0 (95% CI, 2.7-33.0), 2.8 (95% CI, 1.6-5.5), and 4.2 months (95% CI, 2.7-7.2), respectively. Conclusions: In this small study, AEs and tolerability of osimertinib plus selumetinib were as expected, on the basis of 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.
原文英語
頁(從 - 到)4222-4231
頁數10
期刊Clinical Cancer Research
28
發行號19
DOIs
出版狀態已發佈 - 10月 2022
對外發佈

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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