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Combination Therapy for Glioblastoma in Older Patients
New evidence supports combined therapy to improve survival in patients older than 65.
The original phase III trial for treatment of newly diagnosed glioblastoma limited enrollment to patients ≤70 years old, which left open the question of whether combined radiation therapy (RT) with temozolomide (TMZ) was beneficial for patients older than 70. In addition, post hoc subgroup analyses showed that the benefit from adding TMZ lessened with increasing age, leading some to question the value of chemoradiation over single-modality treatment in patients aged 65 to 70.
Now, researchers have conducted a retrospective analysis of treatments for 16,717 patients with glioblastoma aged ≥65 with data in the National Cancer Database, during the period after TMZ came into widespread use. Therapeutic RT was considered to be 10 to 35 fractions, thus including both hypofractionated regimens (1–20 fractions) and standard fractionation regimens (60 Gy delivered over 30 fractions). The analysis shows a clear survival benefit for combined chemoradiation (median overall survival, 9.0 months) over either modality alone (RT, 4.7 months; chemotherapy, 4.3 months). Survival was better with any form of treatment compared with supportive care alone (mean difference, 2.8 months). Importantly, the benefit of combined therapy persisted across all age subgroups and for both biopsy-only patients and those with tumor resection. The data available did not allow subgroup analyses by performance status.
The findings of this well-done analysis support the results from the NCIC-EORTC phase III trial (NCT00482677), presented in oral abstract form at the plenary session of the ASCO 2016 Annual Meeting in early June 2016 (J Clin Oncol 34, 2016 suppl; abstr LBA2). This trial randomized patients aged ≥65 to short-course RT (40 Gy in 15 fractions) alone, versus in combination with concurrent TMZ for 21 days followed by adjuvant TMZ for up to 12 cycles. Combined chemoradiation demonstrated superior survival in the entire patient population. Those with MGMT promoter–methylated tumors particularly benefited but, similar to a previous study of TMZ (N Engl J Med 2005; 352:997), even patients with MGMT promoter–unmethylated tumors had a borderline survival benefit from combined therapy.
Taken collectively, the available data confirm beyond doubt that combined chemoradiation should be the standard of care for all patients with adequate performance status, regardless of age. The only remaining question is whether the length of radiation treatment should be 15 fractions or 30 fractions in older patients.
Jenny Clarke, MD reviewing Rusthoven CG et al. JAMA Neurol 2016 May 23.
Dr. Clarke is Associate Professor of Clinical Neurology and Neurological Surgery, Division of Neuro-oncology, University of California, San Francisco.
Rusthoven CG et al. Combined-modality therapy with radiation and chemotherapy for elderly patients with glioblastoma in the temozolomide era: A National Cancer Database analysis. JAMA Neurol 2016 May 23; [e-pub].
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