Phase II study of oxaliplatin (O) and bevacizumab (B) chemotherapy in refractory germ cell tumors (GCT).

Abstract

e15054 Background: Approximately 80% of patients (pts) with metastatic GCT are cured with first line cisplatin based chemotherapy or subsequent salvage therapy. However, there remains a cohort of pts with incurable refractory and late relapse disease. Single agent O has demonstrated response rate of 13-19% in this setting. VEGF overexpression appears to have a role in GCT progression, and there may be synergy between anti-VEGF therapy and certain cytotoxic agents. This is the first clinical study evaluating B in refractory GCT. Methods: Eligibility required prior cisplatin combination chemotherapy, salvage therapy with high dose chemotherapy (HDC) and prior paclitaxel and gemcitabine. Pts with late relapse or primary mediastinal nonseminomatous GCT (PMNGCT) required failure of at least one prior salvage chemotherapy regimen. Pts received O 85mg/m2 IV and B 10mg/kg IV on a q2wk cycle for up to 14 cycles. Toxicity, response (including serologic) and duration of remission were evaluated. Tumor response was evaluated by RECIST criteria. Serologic response was defined as normalization of markers > 4 wks (CR) and 1 log reduction in hCG or 50% reduction in AFP lasting > 4 wks (PR). Results: Since 11/2006, 19 pts have been enrolled, 18 are evaluable and enrollment continues. Median age was 42y (range 21-55). 2 women with PMNGCT were entered. Median number of prior treatments was 3.5 (range 2-6). There were 8 pts with late relapse and 8 had prior salvage HDC. Therapy was well tolerated. The most common all grade toxicities were nausea (66.7%), sensory neuropathy (61%) and fatigue (55.6%). G3/4 toxicities (seen in late relapse only) were fatigue (11%), pulmonary HTN and laryngitis (6% each). 16 pts were evaluated for serologic response; there were 3 CRs (16.7%) and 3 PRs (16.7%). 10 pts had measurable disease for RECIST evaluation, and no CRs were seen. 1 pt had PR per RECIST and serologic criteria (6%). Median duration of response was 29.3 wks (95% CI 10-36.9). 5 of 8 pts (62.5%) with late relapse responded (3 CR, 2PR). Conclusions: The combination of O+B is well tolerated in a heavily pretreated pt population. The response rate is encouraging when compared to previous trials with O alone. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Biogen Idec, GlaxoSmithKline