A phase II multicenter trial of the multitargeted kinase inhibitor sulfatinib in advanced medullary thyroid cancer (MTC) and radioiodine (RAI)-refractory differentiated thyroid cancer (DTC).

Authors

null

Jiaying Chen

Fudan University Shanghai Cancer Center, Shanghai, China

Jiaying Chen , Qinghai Ji , Junning Cao , Dongmei Ji , Chunmei Bai , Yansong Lin , Bin Pan , Guofang Sun , Jing Li , Chuan Qi , Ye Hua

Organizations

Fudan University Shanghai Cancer Center, Shanghai, China, Phase I Unit, Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China, Peking Union Medical College Hospital, Beijing, China, Hutchision MediPharma Limited, Shanghai, China

Research Funding

Pharmaceutical/Biotech Company

Background: Sulfatinib is an oral tyrosine kinase inhibitor targeting Vascular Endothelial Growth Factor Receptor (VEGFR), Fibroblast Growth Factor Receptor 1 (FGFR 1), and Colony Stimulating Factor 1 Receptor (CSF1R). In a proof of concept (PoC) phase II study, sulfatinib showed promising efficacy in patients (pts) with neuroendocrine tumors (NETs). Methods: This is an open label, two cohorts phase II study using Simon's two-stage design. In stage I, 15 pts will be enrolled in each cohort (advanced MTC or iodine-refractory DTC), and 10 more pts will be enrolled in a cohort in stage II if at least 2 PR observed in that cohort in stage I. Pts are required to have progressive disease in the past 12 months, but could not have received > 1 prior anti-angiogenesis therapy. Pts are treated with oral sulfatinib 300 mg once daily until disease progression, death, or intolerable toxicity. Primary endpoint is Objective Response Rate (ORR) by investigator per RECIST 1.1. Results: As of Dec 31 2016,the studyenrolled 18 pts (MTC: 6, DTC: 12), amongst whom 17 pts were efficacy evaluable. There were a total of 4 confirmed PRs, 1 in the MTC cohort and 3 in the DTC cohort, respectively. The others best response was stable disease (SD). 11 pts (61.1%) had dose interruption due to adverse events (AEs) and 5 pts (27.8%) had dose reduction. Two pts discontinued therapy (1 patient due to disease progression, another due to subject's decision). The most commonly reported AEs were proteinuria 72.2% (Grade 3-4: 22.2%), hypertriglyceridemia 50.0% (Grade 3-4: 0%), hypertension 44.4% (Grade 3-4: 16.7%), blood bilirubin increased 44.4% (Grade 3-4: 5.6%), and diarrhea 33.3% (Grade 3-4: 0%). No Grade 5 AE was reported by the time of data cut-off. Conclusions: Sulfatinib appears to be well tolerated in the pts with advanced MTC and RAI refractory DTC. Safety profile seems to be consistent to previous report, with mostly manageable AEs. Efficacy is encouraging in both indications. Further investigation is warranted. Clinical trial information: NCT02614495

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Head and Neck Cancer

Track

Head and Neck Cancer

Sub Track

Advanced/Metastatic Disease

Clinical Trial Registration Number

NCT02614495

Citation

J Clin Oncol 35, 2017 (suppl; abstr 6037)

DOI

10.1200/JCO.2017.35.15_suppl.6037

Abstract #

6037

Poster Bd #

25

Abstract Disclosures