Sorafenib monotherapy in patients with inoperable/recurrent germ cell tumors (GCT) refractory to chemotherapy: Phase II study.

Abstract

367 Background: The phase II trial was conducted in the population of incurable patients with refractory or relapsed GCT to evaluate the activity of sorafenib, an oral multitarget inhibitor of Raf kinase and the tyrosine kinases VEGFR-2 and PDGFR-alpha. Methods: Patients with progressive metastatic GCT received sorafenib monotherapy continuosly 400mg bid until progression of disease or unacceptable toxicity. Serum tumor markers (STM) were assessed every 4 weeks and imaging was performed every 12 weeks. Responses were assessed using RECIST; STM normalization was required for complete responses and partial responses required at least STM stabilization. STM-only declines were recorded as stable disease. Descriptive analysis of efficacy and tolerance was conducted. Results: 18 male patients with nonseminoma were included between 9/2008 and 6.2010. Pts received median 3 (range 3-4) prior chemotherapy treatments, 2 had received prior high-dose therapy. Median age was 35 (range 26-48), primary site was testicular in 16 and in 2 cases retroperitoneal. All patients had STM elevation before treatment. Median treatment duration was 83 days (31, 617), 12/18 patients were treated more than 2 cycles, 8 pts experienced some degree of STM decline with prolonged SD lasted more than 350 days in 3 pts. No partial or complete responses were observed. Drug related adverse events (AEs) were mainly grade 1 and 2; 55% of patients experienced diarrhea, 44% rash, 55% HFSR, 33% hypertension, 28% fatigue. Some G3 toxicity occurred: diarrhea in one pts, hypertension in one patient, HFSR in 2/18. 31% and 22% of pts required dose interruption and reduction respectively due to AEs. Conclusions: Sorafenib monotherapy was well tolerated but did not demonstrated significant activity in patients with highly refractory GCT, although there were some prolonged SD observed. Clinical trial information: NCT00772694.