Biological basis and early clinical results of immunotherapy for cisplatin-resistant germ cell cancer
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Biological basis and early clinical results of immunotherapy for cisplatin-resistant germ cell cancer. / Oing, Christoph; Bokemeyer, Carsten.
in: CURR OPIN UROL, Jahrgang 28, Nr. 5, 09.2018, S. 479-484.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Review › Forschung
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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 -