Olaparib as a rescue treatment in platinum-refractory germ-cell tumors: the IGG-02 phase II trial.

BACKGROUND

Therapeutic options for patients with advanced germ-cell tumors (GCTs) after multiple relapses or resistant disease are limited. Olaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair.

PATIENTS AND METHODS

In this proof-of principle open-label, single-arm, phase II trial of olaparib 300 mg twice daily in patients with relapsed/refractory metastatic germ-cell cancer [IGG-02 study (NCT02533765)], patient eligibility included failure after high-dose chemotherapy or after at least two different cisplatin-based regimens.

RESULTS

Between September 2015 and February 2019, 18 patients, with a median age of 39 years (range 22-61 years) were enrolled. Severe adverse events (AEs) were observed in seven patients. There were no partial responses, five cases (27.8%) with stable disease (SD) lasting 3, 4, 4, 7 and 43 months, and 13 (72.2%) progressive disease. A germline DNA repair profile panel showed only a BRCA1-mutated case associated with an SD lasting for 4 months. The long-lasting patient on olaparib (43 months) experienced a myelodisplastic syndrome (MDS) associated with the onset of a pathogenic mutation affecting PPM1D.

CONCLUSIONS

Olaparib as a single agent demonstrated no activity in heavily pretreated GCT patients. Future studies with PARP inhibitors should be planned in less-pretreated GCT patients based on molecular analysis to support better patient selection.