Novel therapeutics in refractory germ cell tumors.

Purpose of review: Refractory germ cell tumors (GCT), those progressing after known effective salvage therapies, carry a dismal prognosis with minimal treatment options of limited efficacy. This review aims to highlight the advances in understanding refractory GCT and review upcoming and active clinical trials with novel therapeutics in development.

Recent findings: Patients with refractory disease after optimal salvage chemotherapy are rarely cured and should be referred to centers with expertise in GCT. While prior investigational agents have not overcome current limitations of salvage therapy, current and upcoming trials of novel agents including tyrosine kinase inhibitors (TKI), chimeric antigen receptor (CAR) T-cell therapies, bispecific T-cell engagers (BiTE), and antibody-drug conjugates (ADC) are promising avenues of therapy.

Summary: Outcomes in refractory GCT remain poor. Patients should preferably be evaluated at tertiary care centers with expertise in the management of these patients and access to clinical trials of novel therapeutics. Active research in the understanding of the molecular mechanisms of resistance and targeting of uniquely expressed antigens has broadened the potential therapies in development.