CMTTdb

An integrated database for cancer molecular targeted thearpies

Entry Detail


General information
Database:DB00971
Objective: Foretinib is an oral multikinase inhibitor targeting MET, VEGF, RON, AXL, and TIE2 receptors. Activating mutations or amplifications in MET have been described in patients with papillary renal cell carcinoma (PRCC). they aimed to evaluate the efficacy and safety of foretinib in patients with PRCC.
Authors:Choueiri TK, et al
Title:Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma.
Journal:J Clin Oncol.
Year:2013
PMID:23213094
Trial Design
Clinical Trial Id:NCT00726323
Agent:foretinib
Target:Vascular endothelial growth factor receptor 2
Hepatocyte growth factor receptor
Cancer Type:renal cell carcinoma
Cancer Subtype:papillary renal cell carcinoma
Therapy Type:mono
Therapeutic Combination Type:NA
Therapeutic Combination Content:NA
Study Type:Phase II and biomarker study
Key Patients Feature:patients with papillary renal cell carcinoma (PRCC).
Biomarker:MET pathway activation (germline or somatic MET mutation, MET [7q31] amplification, or gain of chromosome 7).
Biomark Analysis:The presence of a germline MET mutation was highly predictive of a response (five of 10 v five of 57 patients with and without germline MET mutations, respectively).
Control Group Info: cohort A, 240 mg once per day on days 1 through 5 every 14 days (intermittent arm); cohort B, 80 mg daily (daily dosing arm).
Treatment Info:Patients were enrolled onto the study in two cohorts with different dosing schedules of foretinib: cohort A, 240 mg once per day on days 1 through 5 every 14 days (intermittent arm); cohort B, 80 mg daily (daily dosing arm).
Primary End Point: overall response rate (ORR).
Secondary End Point:NA
Patients Number:74
Trial Results
DLT_MTD:NA
Objective Response Rate:13.50%
Disease Control Rate:NA
Median Time to Progression:NA
Median PFS A vs. C: 9.3 months (95% CI, 6.9 to 12.9 months)
Median OS A vs. C:NR(not reached); the 1year survival was 70% overall (64% in the intermittent and 76% in the daily dosing cohort).
Adverse Event(agent arm):The most frequent adverse events of any grade associated with foretinib were fatigue, hypertension, gastrointestinal toxicities, and nonfatal pulmonary emboli.
Conclusions:Foretinib demonstrated activity in patients with advanced PRCC with a manageable toxicity profile and a high response rate in patients with germline MET mutations.