Biological basis and early clinical results of immunotherapy for cisplatin-resistant germ cell cancer

TY - JOUR

T1 - Biological basis and early clinical results of immunotherapy for cisplatin-resistant germ cell cancer

AU - Oing, Christoph

AU - Bokemeyer, Carsten

PY - 2018/9

Y1 - 2018/9

N2 - PURPOSE OF REVIEW: Prognosis of patients with refractory or multiply relapsed germ cell cancer (GCC) is dismal with a life expectancy of a few months only. Thus, new targets and treatment options are urgently needed. Here, we review and discuss the biological basis and first clinical results of immune-checkpoint inhibition by targeting programed death 1 (PD-1) or its ligand (PD-L1) in treatment-refractory GCCs.RECENT FINDINGS: There is a biological rationale to evaluate immune-checkpoint inhibitors in refractory GCCs, as PD-L1 is often expressed and refractory tumors often display mismatch repair deficiency or microsatellite instability. However, the first published clinical phase II trial evaluating pembrolizumab in unselected refractory nonseminoma patients was closed early due to lacking clinical activity. On the contrary, single-case reports have shown meaningful activity in some patients.SUMMARY: To date, targeted treatments, including current immunotherapy approaches, have only shown very limited activity. Although immune-checkpoint inhibition provides an effective treatment option for various malignancies based on large randomized clinical trials, data on the use of this immunotherapy in refractory GCC are scarce as results of ongoing trials are pending.

AB - PURPOSE OF REVIEW: Prognosis of patients with refractory or multiply relapsed germ cell cancer (GCC) is dismal with a life expectancy of a few months only. Thus, new targets and treatment options are urgently needed. Here, we review and discuss the biological basis and first clinical results of immune-checkpoint inhibition by targeting programed death 1 (PD-1) or its ligand (PD-L1) in treatment-refractory GCCs.RECENT FINDINGS: There is a biological rationale to evaluate immune-checkpoint inhibitors in refractory GCCs, as PD-L1 is often expressed and refractory tumors often display mismatch repair deficiency or microsatellite instability. However, the first published clinical phase II trial evaluating pembrolizumab in unselected refractory nonseminoma patients was closed early due to lacking clinical activity. On the contrary, single-case reports have shown meaningful activity in some patients.SUMMARY: To date, targeted treatments, including current immunotherapy approaches, have only shown very limited activity. Although immune-checkpoint inhibition provides an effective treatment option for various malignancies based on large randomized clinical trials, data on the use of this immunotherapy in refractory GCC are scarce as results of ongoing trials are pending.

KW - Antibodies, Monoclonal/therapeutic use

KW - Antibodies, Monoclonal, Humanized/therapeutic use

KW - Antineoplastic Agents, Immunological/therapeutic use

KW - B7-H1 Antigen/metabolism

KW - Cisplatin/therapeutic use

KW - Drug Resistance, Neoplasm

KW - Humans

KW - Lymphocytes, Tumor-Infiltrating/metabolism

KW - Male

KW - Neoplasms, Germ Cell and Embryonal/drug therapy

KW - Nivolumab/therapeutic use

KW - Programmed Cell Death 1 Receptor/metabolism

KW - Testicular Neoplasms/drug therapy

U2 - 10.1097/MOU.0000000000000531

DO - 10.1097/MOU.0000000000000531

M3 - SCORING: Review article

C2 - 29957683

VL - 28

SP - 479

EP - 484

JO - CURR OPIN UROL

JF - CURR OPIN UROL

SN - 0963-0643

IS - 5

ER -