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Cancer. 2015 May 1;121(9):1463-8. doi: 10.1002/cncr.29213. Epub 2014 Dec 18.

Phase 2 trial of the cyclin-dependent kinase 4/6 inhibitor palbociclib in patients with retinoblastoma protein-expressing germ cell tumors.

Author information

1
Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.

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.

KEYWORDS:

PD0332991; cyclin-dependent kinase inhibitor; germ cell tumor; palbociclib; teratoma

PMID:
25522918
DOI:
10.1002/cncr.29213
[Indexed for MEDLINE]
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