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

Aurelio Hernández-Laín, Estela Pineda, Vanessa Pachón, Robert Morales-Llombart, María Cruz Martín-Soberón, Pilar Sánchez-Gómez, Yolanda Ruano, Diana Cantero Montenegro, Laura Oleaga, Manuel Benavides, Miguel Navarro Martín, Amaya Hilario, Juan Manuel Sepúlveda-Sánchez, Guillermo Velasco, José Muñoz-Langa, Ramón De Las Peñas, Gema Durán, Ángel Rodríguez Sánchez, Carlos Mesía Barroso, Elena Vicente, María Ángeles Vaz Salgado, Miriam Alonso-García, Miguel Gil-Gil

Journal: Targeted oncology 2021;15(5):613-622

PMID: 33025213

Full Text on Springer View on PubMed

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).

Address: Medical Oncology Department, Hospital Universitario, 12 de Octubre, Avda. Andalucía s/n, 28041, Madrid, Spain. [email protected].; Medical Oncology Department, Institut Català d'Oncologia L'Hospitalet, L'Hospitalet de Llobregat, Barcelona, Spain.; Medical Oncology Department, Hospital Universitario Virgen del Rocío, Seville, Spain.; Medical Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.; Medical Oncology Department, Hospital Universitario Insular de Gran Canaria, Las Palmas, Spain.; Medical Oncology Department, Hospital Universitario de León, León, Spain.; Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain.; Medical Oncology Department, Consorcio Hospitalario Provincial de Castellón, Castellón, Spain.; Medical Oncology Department, Hospital Universitario y Policlínico La Fe, Valencia, Spain.; Chemical Sciences Faculty, Universidad Complutense de Madrid, Madrid, Spain.; Department of Pathology (Neuropathology), Instituto de Investigaciones Biomédicas I+12, Hospital Universitario, 12 de Octubre, Madrid, Spain.; Radiology Department, Universitary Hospital, 12 de Octubre, Madrid, Spain.; Medical Oncology Department, Hospital Universitario de Salamanca, Salamanca, Spain.; Radiology Department, Hospital Clínic Barcelona, Barcelona, Spain.; Neurooncology (Molecular Biology) Department, Hospital Universitario, 12 de Octubre, Madrid, Spain.; Molecular Pathology Unit, Hospital Universitario 12 de Octubre Research Institute, Madrid, Spain.; Neurooncology Unit, Instituto de Salud Carlos III-UFIEC, Madrid, Spain.; Medical Oncology Department, Hospital Universitario, 12 de Octubre, Avda. Andalucía s/n, 28041, Madrid, Spain.; MFAR Clinical Research, Barcelona, Spain.; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.; Medical Oncology Department, Hospital Clínic, Barcelona, Spain.

DOI: 10.1007/s11523-020-00754-6

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https://dx.doi.org/10.1007/s11523-020-00754-6

MeSH Terms: Adult, Aged, Female, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Oligodendroglioma, Piperazines, Protein Kinase Inhibitors, Pyridines, Retinoblastoma, Treatment Outcome