Phase II Trial of Palbociclib in Recurrent Retinoblastoma-Positive Anaplastic Oligodendroglioma: A Study from the Spanis
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ORIGINAL RESEARCH ARTICLE
Phase II Trial of Palbociclib in Recurrent Retinoblastoma‑Positive Anaplastic Oligodendroglioma: A Study from the Spanish Group for Research in Neuro‑Oncology (GEINO) Juan Manuel Sepúlveda‑Sánchez1 · Miguel Gil‑Gil2 · Miriam Alonso‑García3 · María Ángeles Vaz Salgado4 · Elena Vicente5 · Carlos Mesía Barroso2 · Ángel Rodríguez Sánchez6 · Gema Durán7 · Ramón De Las Peñas8 · José Muñoz‑Langa9 · Guillermo Velasco10 · Aurelio Hernández‑Laín11 · Amaya Hilario12 · Miguel Navarro Martín13 · Manuel Benavides7 · Laura Oleaga14 · Diana Cantero Montenegro15 · Yolanda Ruano16 · Pilar Sánchez‑Gómez17 · María Cruz Martín‑Soberón1 · Robert Morales‑Llombart18 · Vanessa Pachón4 · Estela Pineda19,20 Published online: 6 October 2020 © Springer Nature Switzerland AG 2020
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).
1 Introduction Oligodendroglial tumors are infrequent brain neoplasms characterized by mutations in isocitrate dehydrogenase (IDH) genes and the loss of the chromosomes 1p and 19q. According to the Central Brain Tumor Registry of the United States (CBTRUS), oligodendroglial tumors represent 4.5% of malignant primary brain tumors in
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