GAMMA: Results from a Phase II Study for Relapsed Germ Cell Tumors using an Oxaliplatin-Based Treatment Regimen

Abstract

BACKGROUND: Many patients with relapsed germ cell tumors (GCTs) can still be cured with salvage chemotherapy. Oxaliplatin-based therapies may offer reduced toxicity and noncross resistance to cisplatin-based therapies. PET scan response early during therapy may predict long term outcome. METHODS: Eligible patients with GCTs who progressed following cisplatin-based chemotherapy were recruited into this single-arm, phase II clinical trial. Participants received four 21-day cycles of actinomycin D, methotrexate, paclitaxel, and oxaliplatin. The primary endpoint was objective response rate. Secondary endpoints were progression-free survival (PFS), overall survival and toxicity. A survival analysis was performed based on International Prognostic Factors Study Group (IPFSG) classes. The early predictive value of response on PET CT after 1 cycle of treatment was also assessed. RESULTS: Forty four patients received at least 1 dose of the study medication between 2012 and 2020. The median age was 38, and 70% had intermediate, high or very high-risk disease by IPFSG criteria. The objective response rate of the evaluable population was 59.0%. The median combined radiological or tumor marker PFS was 9.7 months (95% CI, 3.0-22.0 months). At a median follow-up of 26.9 months, the median overall survival was not reached (95% CI, 17.8-NR). Analyses of outcomes based on IPFSG showed relatively favorable outcomes in patients with high and very high-risk disease, with a 2-year combined PFS rates of 33%. PET CT response after 1 cycle of treatment did not predict PFS benefit. CONCLUSIONS: The GAMMA regimen demonstrates encouraging antitumor activity in relapsed GCT, despite recruiting a cohort of patients with predominantly poor risk disease.