ABSTRACT
Background: The addition of bevacizumab to temozolomide-based chemoradiotherapy (TMZ/RT â TMZ) did not prolong overall survival (OS) in patients with newly diagnosed glioblastoma in phase III trials. Elderly and frail patients are underrepresented in clinical trials, but early reports suggested preferential benefit in this population. Patients and methods: ARTE was a 2 : 1 randomized, multi-center, open-label, non-comparative phase II trial of hypofractionated RT (40 Gy in 15 fractions) with bevacizumab (10 mg/kg×14 days) (arm A, N = 50) or without bevacizumab (arm B, N = 25) in patients with newly diagnosed glioblastoma aged ≥65 years. The primary objective was to obtain evidence for prolongation of median OS by the addition of bevacizumab to RT. Response was assessed by RANO criteria. Quality of life (QoL) was monitored by the EORTC QLQ-C30/BN20 modules. Exploratory studies included molecular subtyping by 450k whole methylome and gene expression analyses. Results: Median PFS was longer in arm A than in arm B (7.6 and 4.8 months, P = 0.003), but OS was similar (12.1 and 12.2 months, P = 0.77). Clinical deterioration was delayed and more patients came off steroids in arm A. Prolonged PFS in arm A was confined to tumors with the receptor tyrosine kinase (RTK) I methylation subtype (HR 0.25, P = 0.014) and proneural gene expression (HR 0.29, P = 0.025). In a Cox model of OS controlling for established prognostic factors, associations with more favorable outcome were identified for age <70 years (HR 0.52, P = 0.018) and Karnofsky performance score 90%-100% (HR 0.51, P = 0.026). Including molecular subtypes into that model identified an association of the RTK II gene methylation subtype with inferior OS (HR 1.73, P = 0.076). Conclusion: Efficacy outcomes and exploratory analyses of ARTE do not support the hypothesis that the addition of bevacizumab to RT generally prolongs survival in elderly glioblastoma patients. Molecular biomarkers may identify patients with preferential benefit from bevacizumab. Clinical trial registration number: NCT01443676.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Bevacizumab/therapeutic use , Chemoradiotherapy/mortality , Glioblastoma/drug therapy , Glioblastoma/radiotherapy , Quality of Life , Radiation Dose Hypofractionation , Aged , Aged, 80 and over , Female , Follow-Up Studies , Glioblastoma/pathology , Humans , Male , Prognosis , Survival RateABSTRACT
We compared the treatment modalities as well as the oncologic outcome between young elderly (65-79 years old), elderly (>80 years old) and the reference population (<65 years old.) We reviewed 1047 patients treated between 2002 and 2012. Tumor sites, TNM stages, type of treatment, and the oncologic results are compared with survival statistics. The elderly group was associated with an increase in palliative treatment, more women and advanced T stages. For the 947 patients treated with curative intent, 5 year recurrence free survival was comparable. The overall-survival decreases with the age because of intercurrent deaths. Nevertheless, the treatment efficacy is similar. In conclusion, an advanced age is associated with worse survival, without a decrease in loco-regional control. The chronological age should not be used as a predictive factor for treatment response.
