Phase 2 Trial of the Cyclin-Dependent Kinase 4/6 Inhibitor Palbociclib in Patients With Retinoblastoma Protein-Expressing Germ Cell Tumors

BACKGROUNDAlterations in the retinoblastoma pathway in germ cell tumors (GCTs) have been described. In the phase 1 trials of the selective cyclin-dependent kinase 4/6 inhibitor palbociclib, 3 patients with unresectable, growing, mature teratoma syndrome achieved prolonged disease stabilization. The authors conducted an open-label, phase 2 study to determine the efficacy and safety of palbociclib in patients with incurable, refractory, retinoblastoma protein (pRB)-expressing GCTs. METHODSPatients who had incurable, refractory GCTs that demonstrated pRB expression by immunohistochemistry received oral palbociclib 125 mg daily for 21 days followed by a 7-day break. The primary endpoint was the 24-week progression-free survival (PFS) rate. A 24-week PFS rate 15% was considered promising, and a PFS rate 5% was not considered promising. RESULTSThirty patients received treatment, and 29 were evaluable for the primary endpoint. The estimated 24-week PFS rate was 28% (90% exact confidence interval, 15%-44%). Patients who had teratoma and teratoma with malignant transformation had significantly better PFS than patients who had nonteratomatous GCTs. Toxicity was manageable and was principally hematologic. CONCLUSIONSTreatment with palbociclib was associated with a favorable 24-week PFS rate in patients with refractory, pRB-expressing GCTs. Benefit was mainly observed in patients who had unresectable teratomas and teratomas with malignant transformation. Cancer 2015;121:1463-1468. (c) 2014 American Cancer Society. The retinoblastoma pathway is important in germ cell tumor biology and in the development of the platinum-resistant phenotype. In patients with incurable teratomas, the cyclin-dependent kinase 4/6 inhibitor palbociclib demonstrates promising activity, and further investigation is suggested.