title: Cyclin-Dependent Kinase 4/6 Inhibition for the Treatment of Unresectable Mature Teratoma: Long-Term Follow-Up of a Phase II Study.
abstract: Unresectable mature teratoma is an incurable disease associated with significant morbidity. Given the rarity of the disease, long-term outcomes for patients receiving systemic therapy have not been well described.
  
  
  
  The present study was a retrospective analysis with long-term follow-up data of the patient cohort with unresectable mature teratoma treated in the nonrandomized phase II study of palbociclib for the treatment of metastatic, retinoblastoma protein-expressing refractory germ cell tumors. Patient clinical data were obtained from the medical records and by communication with the enrolled patients and referring medical providers. Major medical events for the treatment of germ cell tumor, including before, during, and after study treatment, were recorded. The major clinical events of interest included the initiation of systemic therapy, radiation therapy, surgical debulking, or other invasive procedures. The study endpoints included the prestudy period and study period clinical event rates, event-free survival, and radiographic progression-free survival.
  
  
  
  Long-term follow-up data were obtained for 12 patients with unresectable mature teratoma. The median prestudy period follow-up period was 19.7 months, and the median study follow-up period was 38.0 months. The median number of palbociclib treatment cycles was 11. The prestudy major clinical event rate was 2.27 events annually (95% confidence interval [CI], 1.66-3.13 events), and the study period event rate was 0.62 events annually (95% CI, 0.36-1.09 events). The median progression-free survival was 5.3 months (95% CI, 1.8-22.6 months), and the median event-free survival duration was 16.2 months (95% CI, 3.0-24.3 months).
  
  
  
  Unresectable mature teratoma is associated with significant long-term cumulative morbidity. The initiation of palbociclib might result in a clinically meaningful delay in disease-related major clinical events. These findings lend further support to the therapeutic activity of cyclin-dependent kinase 4/6 inhibition in this incurable patient population.
authors.affiliation: Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Abramson Cancer Center, University of Pennsylvania, Perelman Center for Advanced Medicine, Philadelphia, PA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Narayan
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Perelman Center for Advanced Medicine, Philadelphia, PA; Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hwang
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Perelman Center for Advanced Medicine, Philadelphia, PA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Priti
authors.initials: P
authors.lastname: Lal
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Perelman Center for Advanced Medicine, Philadelphia, PA; Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rosen
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Perelman Center for Advanced Medicine, Philadelphia, PA.
authors.forename: Maryann
authors.initials: M
authors.lastname: Gallagher
authors.affiliation: Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Abramson Cancer Center, University of Pennsylvania, Perelman Center for Advanced Medicine, Philadelphia, PA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: O'Dwyer
authors.affiliation: Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Abramson Cancer Center, University of Pennsylvania, Perelman Center for Advanced Medicine, Philadelphia, PA. Electronic address: david.vaughn@uphs.upenn.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Vaughn
mesh_terms: D000293:Adolescent; D000328:Adult; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D010879:Piperazines / Q000008:administration & dosage* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage* / Q000627:therapeutic use; D012189:Retrospective Studies; D016019:Survival Analysis; D013724:Teratoma / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; C500026:palbociclib
keywords: Cell cycle; Cyclin-dependent kinases; Germ cell tumor; Palbociclib; Retinoblastoma protein