| Autor: |
Sepúlveda-Sánchez, Juan Manuel, Gil-Gil, Miguel, Alonso-García, Miriam, Vaz Salgado, María Ángeles, Vicente, Elena, Mesía Barroso, Carlos, Rodríguez Sánchez, Ángel, Durán, Gema, De Las Peñas, Ramón, Muñoz-Langa, José, Velasco, Guillermo, Hernández-Laín, Aurelio, Hilario, Amaya, Navarro Martín, Miguel, Benavides, Manuel, Oleaga, Laura, Cantero Montenegro, Diana, Ruano, Yolanda, Sánchez-Gómez, Pilar, Martín-Soberón, María Cruz |
| Zdroj: |
Targeted Oncology; Oct2020, Vol. 15 Issue 5, p613-622, 10p |
| Abstrakt: |
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). [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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