Phase II trial of sorafenib in esophageal (E) and gastroesophageal junction (GEJ) cancer: Response and protracted stable disease observed in adenocarcinoma.

Abstract

4100 Background: Sorafenib is a tyrosine kinase inhibitor targeting VEGFr, PDGFr, Raf and other pathways. Encouraging response and survival were observed in a phase II trial combining sorafenib with chemotherapy in GE cancer (J Clin Oncol 27:2947;2010). We are studying single agent sorafenib in a phase II trial with the primary endpoint to assess progression-free survival (PFS). Secondary endpoints include response and therapy tolerance. Methods: Patients (pts) with measurable metastatic E and GEJ cancer with no more than 3 prior chemotherapy regimens were treated with sorafenib 400 mg BID. CT scans were performed monthly for the first 2 months, then every 2 months. Results: Twenty of 35 pts have been accrued and 16 are currently evaluable, 17 male, 3 female, median KPS 80%, age 59, GEJ 6, E 14, squamous 2, adenocarcinoma (AC) 18. An ongoing complete response (15+ months) was observed in a pt with biopsy proven metastatic neck lymphadenopathy (E primary AC, recurrence after prior chemoradiotherapy and surgery). A second pt (GEJ AC) had protracted stable disease in bulky celiac node disease (19+ months). Grade 3 toxicity was limited to skin rash (1 pt), hand foot reaction (2 pt), and fatigue (1 pt). Only 4 of 16 pts (25%) had early disease progression at 2 months or less. Median PFS 3.7 mos, 4 patients (25%) received drug for more than 7 months. The majority of tumors tested positive for phospho-erk by immunohistochemistry (14/17, 75%). Conclusions: The observation of a durable complete response and protracted stable disease to sorafenib in E cancer is remarkable. Further accrual continues to define PFS. Supported by a grant from Bayer.