Phase II study of sunitinib malate in refractory germ cell tumors.

Abstract

e15017 Background: Patients (pts) with platinum-refractory germ cell tumors (GCT) have very poor prognosis. Induction of angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) overexpression was most often seen in teratoma components of GCT. We hypothesized that inhibition of angiogenesis by multikinase oral inhibitor sunitinib could improve prognosis of these pts. The aim of the study was to investigate efficacy and toxicity of sunitinib in refractory GCT. Methods: Sunitinib was administered at a dose of 50mg daily for 4 weeks followed by 2 weeks off therapy. The response was evaluated every 12 weeks in a one-stage phase II trial. The primary end-point was 12-month post-treatment-initiation continuous progression-free survival (PFS) with type I and type II errors of <10%. For such study design 28 patients were planned for inclusion. Results: Ten patients were included in the trial from July 2008 till December 2010. Median age was 32 years (range: 19-55). With the exception of one patient, all were platinum-refractory. Patients were pretreated with median of 3 cisplatin-containing therapies (range: 3-6). The treatment was generally well tolerated. Toxicity grade 3 was the worst experienced toxicity (trombocytopenia in 2 pts, anemia in 1 pt and nausea and vomiting in 1 pt). Median follow-up has been 13 weeks (range: 5 - 47 weeks) and median follow-up of pts still alive has been 26 weeks (range: 5 - 47 weeks). A12-week PFS was 20%. Median PFS and overall survival was 10.8 and 13.1 weeks, respectively. One patient with teratocarcinoma achieved partial remission (PR) in lung, retroperitoneal lymph nodes, and decrease in AFP after two treatment-cycles but progressed after 4 cycles. Another patient with teratoma in primary tumor, but with high level of b-HCG at relapse, achieved PR in lung and lymph nodes after two treatment cycles, however with rapid elevation of b-HCG. Conclusions: Consistently with previous reports, we conclude that monotherapy with sunitinib has limited efficacy in heavily pretreated, unselected, refractory GCTs. Based on our observations we suggest that there might be some efficacy of sunitinib in GCTs with teratoma components that is in concordance with reported overexpression of VEGF in teratoma.