Phase 2 trial of the cyclin‐dependent kinase 4/6 inhibitor palbociclib in patients with retinoblastoma protein‐expressing germ cell tumors. Issue 9 (18th December 2014)

• Record Type: Journal Article
• Authors: Vaughn, David J.; Hwang, Wei‐Ting; Lal, Priti; Rosen, Mark A.; Gallagher, Maryann; O'Dwyer, Peter J.
• Is Part Of: Cancer. Volume 121:Issue 9(2015)
• Page Start: 1463
• Page End: 1468
• Publication Date: 2014-12-18
• Subjects: teratoma -- germ cell tumor -- PD0332991 -- cyclin‐dependent kinase inhibitor -- palbociclib; Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.29213
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract : BACKGROUND: Alterations 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. METHODS: Patients 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. RESULTS: Thirty 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. CONCLUSIONS: Treatment 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. © 2014 American Cancer Society . Abstract : 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.