Radiation Plus Chemotherapy May Boost Elderly Glioblastoma Overall Survival

Glioblastoma patients aged over 65 years may benefit from a combined treatment approach

medwireNews: Cohort study findings support combined-modality therapy (CMT) for elderly patients with glioblastoma, demonstrating a significant overall survival (OS) benefit compared with radiation or chemotherapy given alone.

“These results imply that the Stupp protocol of CMT with temozolomide, now used as the standard of care for patients younger than 65 years, should be considered in patients older than 65 years”, writes Stephen Clark, from Vanderbilt University Medical School in Nashville, Tennessee, USA, in an editorial accompanying the report published in JAMA Neurology.

And he adds: “Pending the results of the NCT00482677 randomized trial, treatment with CMT in elderly patients with a high [Karnofsky performance status] remains a reasonable option.”

The National Cancer Database analysis collated information on 16,717 patients aged 65 years or older who were diagnosed with glioblastoma between 2005 and 2011, described by the study authors as the “temozolomide era”.

OS was a median 9.0 months for the 8435 patients who received radiotherapy and chemotherapy. This was significantly higher than that achieved by the 1693 patients given only radiotherapy and the 1018 patients given only chemotherapy, at a comparable 4.7 and 4.3 months, respectively. OS fell to a median of just 2.8 months for the 5571 patients given no treatment.

Chad Rusthoven, from the University of Colorado School of Medicine in Aurora, USA, and co-authors emphasize that there was a “consistent OS advantage” with CMT over single modality therapy.

They found that OS remained significantly better with CMT than either radiotherapy or chemotherapy alone in both multivariate analysis (hazard ratio=1.47 and 1.50, respectively) and propensity score-matched analysis accounting for age, comorbidity score and resection.

And subgroup analysis confirmed that CMT offered better OS across all age groups (65–69, 70–74, 75–79 and 80 years and older) and regardless of whether a patient also underwent resection.

“Conversely, no significant differences in OS were observed in multivariate, propensity score-matched analyses, or subgroup analyses between the single-modality treatment strategies involving [radiotherapy] alone vs [chemotherapy] alone”, the researchers add.

Stephen Clark notes that MGMT promoter methylation has been linked to survival in patients treated with temozolomide and that global methylation may be a better marker of interpatient heterogeneity than traditional factors such as age and performance status.

Highlighting the under-representation of elderly patients in glioblastoma clinical trials, and sometimes under-treatment of patients due to toxicity concerns, he concludes that researchers should reconsider using age as a strict cutoff for eligibility for study participation.

References

Rusthoven CG, Koshy M, Sher DJ, 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; Advance online publication 23 May. doi:10.1001/jamaneurol.2016.0839

Clark SW. The age factor in the treatment of glioblastoma. JAMA Neurol 2016; Advance online publication 23 May. doi:10.1001/jamaneurol.2016.1331

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