Investigational targeted therapies for the treatment of testicular germ cell tumors.
BACKGROUND
Germ cell tumors (GCTs) are the most common malignancy among men aged between 15 to 45. Despite high cure rates of >90% over all GCTs, 3 to 5% of patients will still die of platinum-refractory disease. New systemic treatment options are needed to improve treatment success in this challenging setting.


METHODS
To review targeted treatment options and preclinical developments in platinum-refractory GCTs, a comprehensive literature search of PubMed, Medline and scientific meeting abstracts on published clinical trials and reports on molecularly targeted approaches was conducted. Outcomes of platinum-refractory disease and of patients failing high-dose chemotherapy remain poor. Currently, no molecularly targeted treatment has shown clinically meaningful activity in unselected patient populations in clinical trials, but individual patients may achieve short-lived objective responses by treatment with sunitinib, brentuximab vedotin or imatinib. Targeted trials based on molecular selection of patients have not yet been performed.


CONCLUSIONS
The limited activity of targeted agents in refractory GCT is disappointing. Assessment of druggable biomarkers and marker-stratified treatment may help individual patients, but is largely lacking. The low incidence and high curability of GCTs make the design of larger clinical trials difficult. The potential of novel agents, i.e. immune-checkpoint inhibitors, remains to be elucidated.
a Department of Oncology, Hematology and Bone Marrow Transplantation , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
Christoph
C
Oing
b Division of Medical Oncology, British Columbia Cancer Agency Vancouver Cancer Center , University of British Columbia , Vancouver , Canada.
Christian
C
Kollmannsberger
a Department of Oncology, Hematology and Bone Marrow Transplantation , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
Karin
K
Oechsle
a Department of Oncology, Hematology and Bone Marrow Transplantation , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
Carsten
C
Bokemeyer
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods*; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D043823:Taxoids; C552428:cabazitaxel
Germ cell tumor; platinum-refractory disease; targeted therapy; testicular cancer