Phase-2 trial of palbociclib in adult patients with recurrent RB1-positive glioblastoma

J Neurooncol. 2018 Nov;140(2):477-483. doi: 10.1007/s11060-018-2977-3. Epub 2018 Aug 27.


Introduction: Alterations in the CDK4/6-RB signaling pathway are common causes of cell cycle dysregulation in many cancers, including glioblastoma. Palbociclib is an oral inhibitor of CDK4/6, which leads to phosphorylation of RB1 and cell-cycle arrest. We conducted a two-arm study evaluating efficacy and tissue pharmacokinetics/pharmacodynamics of palbociclib in patients with recurrent glioblastoma.

Methods: Eligibility criteria included confirmation of RB1 proficiency by IHC; ≤ 3 relapses; KPS ≥ 60; no limit on prior treatments. Arm 1 received palbociclib for 7 days prior to indicated resection followed by adjuvant palbociclib. Arm 2 received palbociclib without resection. Primary objective was PFS6; secondary included toxicity, OS, and ORR. Exploratory aims included biomarker assessment and pharmacokinetic/pharmacodynamic effects in surgical patients.

Results: Total of 22 patients were enrolled; 6 on Arm 1 and 16 on Arm 2. Trial was stopped early secondary to lack of efficacy, with 95% of evaluable patients progressing within 6 months. Median PFS was 5.14 weeks (range 5 days-142 weeks) and median OS was 15.4 weeks (range 2-274 weeks). Two patients (10%) had related grade ≥ 3 AEs. In Arm 1, 5 patients had tissue concentrations of palbociclib felt to be sufficient for biological effect and paired samples available for RB1 IHC. There were no consistent changes in RB1 expression or cell proliferation in the paired tissue.

Conclusion: In this trial, despite adequate tissue PK, palbociclib monotherapy was not an effective treatment for recurrent glioblastoma. However, these were heavily pretreated patients and targeting the CDK4/6 pathway may still deserve further exploration.

Trial registration: NCT01227434.

Keywords: CDK4/6 inhibitor; Palbociclib; Recurrent glioblastoma; Retinoblastoma pathway.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents / toxicity
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / surgery
  • Combined Modality Therapy
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / surgery
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / surgery
  • Piperazines / pharmacokinetics
  • Piperazines / therapeutic use*
  • Piperazines / toxicity
  • Pyridines / pharmacokinetics
  • Pyridines / therapeutic use*
  • Pyridines / toxicity
  • Young Adult


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Piperazines
  • Pyridines
  • palbociclib

Associated data