Bevacizumab plus hypofractionated radiotherapy versus radiotherapy alone in elderly patients with glioblastoma: Efficacy and imaging analyses of the ARTE trial.

Authors

null

Hans-Georg Wirsching

Department of Neurology, University Hospital, Zürich, Switzerland

Hans-Georg Wirsching , Ghazaleh Tabatabai , Ulrich Roelcke , Andreas Felix Hottinger , Andrea Schmid , Ludwig Plasswilm , Katrin Lisa Conen , Thomas Hundsberger , Francesca Caparrotti , Roger Von Moos , Christian Alexander Riklin , Luca Remonda , Patrick Roth , Leonhard Held , Elisabeth Jane Rushing , Adrian Ochsenbein , Michael Weller

Organizations

Department of Neurology, University Hospital, Zürich, Switzerland, Brain Tumor Center, Kantonsspital Aarau, Aarau, Switzerland, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, Department of Medical Oncology, Bern, Switzerland, Department of Radiation-Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland, University Hospital Basel, Riehen, Switzerland, Department of Neurology, Kantonsspital St. Gallen, St. Gallen, Switzerland, Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland, Department of Medical Oncology, Kantonsspital Graubuenden, Chur, Switzerland, Department of Medical Oncology, Kantonsspital Luzern, Lucerne, Switzerland, Department of Neuroradiology, Kantonsspital Aarau, Aarau, Switzerland, Biostatistics Department, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland, University Hospital Zurich, Department of Neuropathology, Zurich, Switzerland, Inselspital, Bern, Switzerland, Laboratory of Molecular Neuro-Oncology, Department of Neurology, and Neuroscience Center Zurich, University Hospital and University of Zurich, Zurich, Switzerland

Research Funding

Pharmaceutical/Biotech Company

Background: The addition of bevacizumab (BEV) to first-line temozolomide chemoradiotherapy prolonged progression-free survival (PFS), but not overall survival (OS) in newly diagnosed glioblastoma in two phase III trials. Elderly and frail patients are underrepresented in most clinical trials, but early uncontrolled reports of BEV treatment of glioblastoma suggested preferential benefit in this patient population. Methods: ARTE was a 2:1 randomized, multi-center, open-label trial of hypofractionated radiotherapy (RT) in combination with intravenous BEV every 2 weeks (Arm A, N = 50) versus RT alone (Arm B, N = 25) in patients with newly diagnosed glioblastoma aged 65 years or older. Quality of life (QoL) was monitored by the EORTC QLQ-C30/BN20 modules. Response was assessed using Response Assessment in Neuro-Oncology (RANO) criteria. Exploratory imaging studies included apparent diffusion coefficient (ADC) mapping and 18F-fluoro-ethyl-tyrosine (FET) positron emission tomography (PET). Results: Established prognostic factors including age, Karnofsky performance score (KPS), O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation and steroid intake at study entry were balanced between arms. Median PFS was longer in Arm A vs. Arm B (7.6 vs. 4.8 months, p = 0.003), but OS was similar (12.1 vs 12.2 months, p = 0.8). Prior to progression, no differences in QoL were noted, but clinical deterioration was deferred in Arm A vs. Arm B. In a Cox model that controlled for established prognostic factors, an association with prolonged PFS was detected for Arm A versus Arm B (hazard ratio [HR] 0.36, p = 0.001) and for KPS 90-100% versus 60-80% (HR 0.50, p = 0.02). Applying a similar Cox model to OS detected an association with age 65-69 vs 70+ (HR 0.52, p = 0.02) and KPS 90-100% versus 60-80% (HR 0.53, p = 0.03). Exploration of imaging predictors of OS for Arm A identified response by RANO (HR 0.52, p = 0.02), but detected no prognostic role for T2, ADC or FET signal intensity. Conclusions: Efficacy outcomes and exploratory imaging analyses of the ARTE trial do not support the notion that benefit from BEV is more pronounced in elderly glioblastoma patients. Clinical trial information: NCT01443676

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Central Nervous System Tumors

Track

Central Nervous System Tumors

Sub Track

Central Nervous System Tumors

Clinical Trial Registration Number

NCT01443676

Citation

J Clin Oncol 35, 2017 (suppl; abstr 2014)

DOI

10.1200/JCO.2017.35.15_suppl.2014

Abstract #

2014

Poster Bd #

256

Abstract Disclosures

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