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

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.