Abstract B6: A phase II study of the efficacy and safety of foretinib, a novel receptor tyrosine kinase inhibitor, given on an intermittent 5-days-on/9-days-off (5/9) schedule in patients with recurrent or metastatic squamous cell cancer of the head and neck

Abstract

Abstract Foretinib (also known as GSK1363089 and XL880) is a small-molecule, spectrum-specific receptor tyrosine kinase inhibitor, with potent activity against MET, VEGFR2, and multiple additional tyrosine kinases with tumor growth-promoting and angiogenic properties. Antitumor activity has been observed in 2 previous phase I studies. This phase II study was conducted to evaluate responses in squamous cell cancer of the head and neck (SCCHN). An open-label, single-arm, multicenter trial employing a Simon 2-stage design was conducted, with a total of 41 patients to be enrolled in the study. One or more responses in the first 14 subjects were required to progress to the second stage. Foretinib was administered as a 240-mg oral dose once daily on days 1–5 of a 14-day cycle to subjects with recurrent and/or metastatic SCCHN. Other eligibility requirements included measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 1 or 0, and no history of uncontrolled tumor bleeding. Exclusions included more than 1 prior therapy for recurrent or metastatic disease, history of brain metastasis, and rapid progression within 6 months after curative-intent therapy for local/loco-regional disease. Endpoints were objective response rate, safety, duration of response, progression-free survival (PFS), overall survival (OS), and characterization of the pharmacokinetics. Tumor volume was assessed every 8 weeks by Response Evaluation Criteria in Solid Tumors. This study did not meet the predefined criteria for continuing to the second stage. Response and safety data are available for 14 patients with a data cut off date of July 24 2009 (median age = 59.0; males/female = 13/1: ECOG PS 0/1 = 9/5 patients). A maximum of 30 cycles was administered (median = 4.5). The most common reason for withdrawal was progressive disease. Treatment-emergent adverse events occurring in >25% of individuals included (# [%]): fatigue (7 [50%]), constipation (5 [36%]), hypertension (5 [36%]), anorexia (4 [29%]), dysphagia (4 [29%]), weight loss (4 [29%]), increased alanine transaminase (4 [29%]), increased aspartate transaminase (4 [29%]), dyspnea (4 [29%]), headache (4 [29%]), and mucosal inflammation (4 [29%]). Investigator-assessed median PFS (95% confidence interval) was 3.65 (3.42, 5.32) months; median OS was 5.59 (3.71, not reported) months. The best overall response was stable disease (SD), with a median duration of 4.11 (3.65–13.86) months. Foretinib 240 mg on a 5/9 schedule was generally well tolerated. SD was the best observed response. The safety and efficacy results support further investigation in combination with other targeted agents or cytotoxic chemotherapy. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B6.