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

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


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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / mortality
  • Piperazines / pharmacology
  • Piperazines / therapeutic use*
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*
  • Retinoblastoma Protein / metabolism*
  • Teratoma / drug therapy*
  • Teratoma / metabolism
  • Teratoma / mortality
  • Testicular Neoplasms / drug therapy*
  • Testicular Neoplasms / metabolism
  • Testicular Neoplasms / mortality
  • Treatment Outcome
  • Young Adult


  • Antineoplastic Agents
  • Piperazines
  • Pyridines
  • Retinoblastoma Protein
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • palbociclib