Phase II Trial of Palbociclib in Recurrent Retinoblastoma-Positive Anaplastic Oligodendroglioma: A Study from the Spanish Group for Research in Neuro-Oncology (GEINO).

Abstract

BACKGROUND:

The cell cycle checkpoint G1/S, dependent on cyclin-dependent kinase (CDK) 4 amplification/overexpression and retinoblastoma phosphorylation, is altered in most anaplastic oligodendrogliomas (AOs).

OBJECTIVE:

We aimed to evaluate the efficacy of palbociclib, an oral inhibitor of CDK4/6 with proven efficacy in breast cancer, in patients with AO. The primary endpoint was progression-free survival at 6 months.

PATIENTS AND METHODS:

We conducted a multicenter, open-label, phase II trial evaluating the efficacy and safety of palbociclib in patients with AO who progressed on radiotherapy and chemotherapy with histologically and molecularly confirmed grade 3 oligodendroglioma and conserved retinoblastoma protein (pRb) expression by immunohistochemistry. Patients were treated with palbociclib (125 mg/day) for 3/1 weeks on/off.

RESULTS:

Overall, 34 patients were enrolled across 10 hospitals in the Spanish Group of Neuro-Oncology (GEINO) study. The study was stopped early owing to the lack of efficacy, with 74% of evaluable patients progressing within 6 months, which was insufficient to consider palbociclib as an active drug in this population. Within the median follow-up of 12 months, the median progression-free survival was 2.8 months [95% confidence interval (CI) 2.6-3.1] and the median overall survival was 32.1 months (95% CI 5.1-59.2). There were no partial or complete responses; only 13 patients (38%) achieved stable disease as the best response. Palbociclib was well tolerated, with neutropenia (grade 3 or higher: 58.8%) and thrombocytopenia (grade 3 or higher: 14.7%) as the most common adverse events (AEs). Both AEs had no significant impact.

CONCLUSION:

Despite the good tolerance, palbociclib monotherapy did not show favorable efficacy against recurrent AO.

TRIAL REGISTRATION:

This study is registered with ClinicalTrials.gov, identifier NCT0253032 (retrospectively registered on 21 August 2015).

• Authors: Juan Manuel Sepúlveda-Sánchez, Miguel Gil-Gil, Miriam Alonso-García, María Ángeles Vaz Salgado, Elena Vicente, Carlos Mesía Barroso, Ángel Rodríguez Sánchez, Gema Durán, Ramón De Las Peñas, José Muñoz-Langa, Guillermo Velasco, Aurelio Hernández-Laín, Amaya Hilario, Miguel Navarro Martín, Manuel Benavides, Laura Oleaga, Diana Cantero Montenegro, Yolanda Ruano, Pilar Sánchez-Gómez, María Cruz Martín-Soberón, Robert Morales-Llombart, Vanessa Pachón, Estela Pineda
• Journal: Targeted oncology (Target Oncol) Vol. 15 Issue 5 Pg. 613-622 (10 2020) ISSN: 1776-260X [Electronic] France
• PMID: 33025213 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Piperazines
• Protein Kinase Inhibitors
• Pyridines
• palbociclib

Topics

• Adult
• Aged
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Oligodendroglioma (drug therapy, pathology)
• Piperazines (pharmacology, therapeutic use)
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Pyridines (pharmacology, therapeutic use)
• Retinoblastoma (drug therapy, pathology)
• Treatment Outcome