Abstract CT081: High-dose chemotherapy associated with bevacizumab for metastatic germ cell tumors: the TAXIF 3 trial

Abstract

Abstract Germ cell tumors (GCT) are a model of curative disease. 5-year overall survival (OS) rates for metastatic patients, reach, according to prognosis, 92% (good), 80% (intermediate) and 48% (poor). The current first-line therapy is the combination of bleomycin, etoposide, and cisplatin (BEP). Despite the high cure rate of BEP, 10 to 20% of patients relapse. Those patients are then candidates for initial salvage therapy with VeIP (vinblastine-ifosfamide-cisplatin), VIP (VeIP with etoposide in place of vinblastine), or a combination of ifosfamide and platinum salts with paclitaxel (TIP). Another option is intensification therapy. We previously developed two clinical trials (TAXIF 1, TAXIF 2) using three sequential cycles of high-dose chemotherapy (HDCT) with autologous hematopoietic stem-cell transplant (HSCT). These approaches showed encouraging activity in both relapsed and refractory patients. However, they did not prevent emergence of resistance and, for many patients, disease progressed. To improve outcomes, we set up the TAXIF 3 clinical trial (ClinicalTrials.gov Identifier NCT01966913). Its rational explores both the mechanisms of disease etiology and drug resistance. In particular, as angiogenesis plays a functional role in testicular GCTs growth and progression and is an indicator of metastatic disease, we decided to combine HDCT with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab. Importantly, the TAXIF 3 trial includes administration, in a unique way, of semi-intensive doses of the epirubicin-paclitaxel (EPI-TAX) combination prior to HDCT. Not only the EPI-TAX regimen is crucial to mobilize and collect an adequate number of hematopoietic stem-cells, it also, plays an important role in sensitizing patients to chemotherapy before HDCT. TAXIF 3 is a multicentric phase II study supported by the French Ministry of Health. It started in October 2013 and is still recruiting patients. The main eligibility criteria are: age ?18 years old, GCTs patients with any histology (seminoma and nonseminoma) who failed chemotherapy platinum-based (relapsed sensitive/resistant or refractory). Initially, patients are treated with 2-4 courses of front-line EPI-TAX (epirubicin 100mg/m2; paclitaxel 250mg/m2). Then, the responders are scheduled to receive two cycles of HDCT (ICE: ifosfamide 12,000mg/m2; carboplatin AUC20; etoposide 1500mg/m2) supported by HSCT. Bevacizumab (7.5mg/Kg) is administered before and after each HDCT cycle. The primary objective is complete response rate. Secondary end points are overall response rates, progression-free and OS. Besides the clinical approach, the TAXIF 3 also aims at identifying predictive biomarkers to monitor and select patients. Statistical analyses are performed through a Bayesian approach. The study planned to include 50 patients. To date, the trial has so included about 50% of the expected patients. Citation Format: Frédéric Selle, Joseph Gligorov, Lionel Geoffrois, Stéphane Provent, Benjamin Laverdant, Yohann Dabi, Anne Kieffer, Daniele G. Soares, Jean-Pierre Lotz. High-dose chemotherapy associated with bevacizumab for metastatic germ cell tumors: the TAXIF 3 trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT081.