https://scholars.lib.ntu.edu.tw/handle/123456789/557714
標題: | TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer | 作者: | Oxnard G.R. CHIH-HSIN YANG Yu H. Kim S.-W. Saka H. Horn L. Goto K. Ohe Y. Mann H. Thress K.S. Frigault M.M. Vishwanathan K. Ghiorghiu D. Ramalingam S.S. Ahn M.-J. |
關鍵字: | combination; EGFR mutation; non-small cell lung cancer; osimertinib; phase I | 公開日期: | 2020 | 出版社: | Elsevier Ltd | 卷: | 31 | 期: | 4 | 起(迄)頁: | 507-516 | 來源出版物: | Annals of Oncology | 摘要: | Background: Osimertinib is a potent, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The multi-arm phase Ib TATTON study (NCT02143466) was designed to assess the safety and tolerability of osimertinib in combination with other targeted therapies: selumetinib (MEK1/2 inhibitor), savolitinib (MET-TKI), or durvalumab [anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibody]. Patients and methods: Patients with advanced EGFR-mutant non-small-cell lung cancer and disease progression on a prior EGFR-TKI were enrolled and allocated to dose-escalating cohorts combining osimertinib 80 mg orally (p.o.) once a day with selumetinib (25–75 mg p.o. twice a day; continuous or intermittent), savolitinib (600–800 mg p.o. once a day), or durvalumab (3–10 mg/kg intravenous every 2 weeks). Results: At data cut-off (28 February 2018), 77 patients were enrolled and received osimertinib plus selumetinib (n = 36), savolitinib (n = 18), or durvalumab (n = 23). Most common adverse events (any grade), occurring in ?20% of patients across dose groups, were: selumetinib arm—diarrhea (75%), rash (58%), nausea (47%); savolitinib arm—nausea (67%), rash (56%), vomiting (50%); durvalumab arm—rash (48%), vomiting (43%), diarrhea (39%). Dose-limiting toxicities were reported in the selumetinib 25 mg (n = 1), 50 mg (n = 1), and 75 mg (n = 4) continuous-dose groups, savolitinib 600 mg (n = 1) and 800 mg dose groups (n = 2), and durvalumab 10 mg/kg (n = 1) dose group. The objective response rate was 42% (95% confidence interval 26% to 59%), 44% (22% to 69%), and 43% (23% to 66%) in the selumetinib, savolitinib, and durvalumab arms, respectively. Conclusion: Our results demonstrate the feasibility of combining osimertinib 80 mg with selumetinib or savolitinib at identified tolerable, active doses. A combination of osimertinib with durvalumab was not feasible due to increased reporting of interstitial lung disease. Osimertinib-based combination therapies represent a compelling approach now being further investigated. Clinical trials number: NCT02143466. ? 2020 European Society for Medical Oncology |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85080946485&doi=10.1016%2fj.annonc.2020.01.013&partnerID=40&md5=cb3611fd67f3e515edbca1f1c600bb79 https://scholars.lib.ntu.edu.tw/handle/123456789/557714 |
ISSN: | 0923-7534 | DOI: | 10.1016/j.annonc.2020.01.013 | SDG/關鍵字: | alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; durvalumab; epidermal growth factor receptor; osimertinib; programmed death 1 ligand 1; savolitinib; scatter factor receptor; selumetinib; 1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine; acrylamide derivative; aniline derivative; antineoplastic agent; benzimidazole derivative; durvalumab; EGFR protein, human; epidermal growth factor receptor; monoclonal antibody; osimertinib; protein kinase inhibitor; pyrazine derivative; selumetinib; triazine derivative; adult; aged; anemia; Article; asthenia; constipation; controlled clinical trial; controlled study; coughing; decreased appetite; dermatitis; diarrhea; dizziness; drug dose escalation; drug intermittent therapy; drug safety; drug tolerability; drug withdrawal; dry skin; dyspnea; fatigue; female; fever; gene mutation; headache; human; hyperglycemia; hypertransaminasemia; hypoalbuminemia; hyponatremia; interstitial lung disease; leukocyte count; lung embolism; major clinical study; male; molecularly targeted therapy; multicenter study; nausea; neutropenia; neutrophil count; non small cell lung cancer; open study; paronychia; peripheral edema; phase 1 clinical trial; pneumonia; priority journal; pruritus; rash; side effect; stomatitis; thrombocytopenia; vomiting; clinical trial; genetics; lung tumor; mutation; Acrylamides; Aniline Compounds; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Pyrazines; Triazines |
顯示於: | 腫瘤醫學研究所 |
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