title: Phase 2 trial of the cyclin-dependent kinase 4/6 inhibitor palbociclib in patients with retinoblastoma protein-expressing germ cell tumors.
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.
authors.affiliation: Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: David J
authors.initials: DJ
authors.lastname: Vaughn
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hwang
authors.forename: Priti
authors.initials: P
authors.lastname: Lal
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rosen
authors.forename: Maryann
authors.initials: M
authors.lastname: Gallagher
authors.forename: Peter J
authors.initials: PJ
authors.lastname: O'Dwyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D013724:Teratoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D010879:Piperazines; D011725:Pyridines; D016160:Retinoblastoma Protein; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; C500026:palbociclib
keywords: PD0332991; cyclin-dependent kinase inhibitor; germ cell tumor; palbociclib; teratoma