Chemoradiation Boosts Survival in Elderly Glioblastoma Patients

Roxanne Nelson, BSN, RN

March 15, 2017

Adding temozolomide (Temodar, Merck) to radiotherapy in elderly glioblastoma patients increases survival when compared to radiotherapy alone and is a new standard of care, according to investigators.

The combination has been standard in younger patients for a decade, and now, for the first time, it has been proven superior to radiation alone in elderly patients.

In the new study, chemoradiation improved both overall and progression-free survival, but the benefits were most pronounced in patients with methylation of the O6-methylguanine–DNA methyltransferase (MGMT) gene promoter region, a genetic abnormality linked to better response to chemotherapy and longer survival for patients with this disease.

The results were initially presented during the plenary session of the annual meeting of the American Society of Clinical Oncology and were reported by Medscape Medical News at that time.

They have now been published in the March 16 issue of the New England Journal of Medicine.

"Although glioblastoma disproportionately affects older patients, there are no clear guidelines for treating these patients, and practice varies globally," said lead author James R. Perry, MD, from the Sunnybrook Health Sciences Center in Toronto, Canada, during his presentation.

"This study provides the first evidence from a randomized clinical trial that chemotherapy in combination with a shorter radiation schedule significantly extends survival without a detriment to quality of life," Dr Perry explained.

Other research has shown that among younger patients (aged 70 years or younger), adding temozolomide to standard radiotherapy (60 Gy over a period of 6 weeks) confers a survival advantage.

For older patients, however, shorter courses of radiotherapy are more common, but it has been unclear whether adding temozolomide to a shorter course of radiotherapy would confer a survival advantage in this population.

Better Survival for Combination Therapy

To evaluate the use of combination therapy in this population, Dr Perry and his colleagues randomly assigned 562 patients aged 65 years or older who had been newly diagnosed with glioblastoma to receive either radiotherapy alone (40 Gy in 15 fractions) or radiotherapy with concomitant and adjuvant temozolomide.

The median age of the cohort was 73 years (range, 65 to 90 years). In addition, 165 patients had MGMT promoter methylation.

Nearly the entire cohort was followed until death. For the small number who survived, the median follow-up was 17 months.

The median overall survival was significantly better in the group that received combination therapy: 9.3 months with radiotherapy plus temozolomide, and 7.6 months with radiotherapy alone. This extrapolated to a 33% decrease in the risk for death (hazard ratio [HR], 0.67; P < .001).

The authors found that for patients who had undergone biopsy only, survival was shorter in comparison with those patients who had undergone partial or complete resection (HR for death, 1.67; P < .001).

Patients with higher Mini–Mental State Examination scores experienced increased survival in comparison with patients with lower scores (HR for death with a 1-unit increase as continuous variable, 0.96; 95% CI, 0.94 - 0.98; P < .001).

Differences in Subgroups

On analysis with respect to age groups, survival differences were observed. For patients aged 65 to 70 years, the median overall survival was 8.7 months with radiotherapy plus temozolomide and 8.3 months with radiotherapy alone (HR for death, 0.93).

For those aged 71 to 75 years, the difference was more pronounced: 9.3 months vs 7.6 months (HR, 0.63).

The difference was greatest in the oldest cohort (76 years of age or older): 10.0 months vs 7.1 months (HR, 0.53).

The greatest survival benefit was seen among the 165 patients with MGMT status. Overall survival almost doubled with the addition of temozolomide to the radiation therapy regimen: 13.5 months with chemoradiation vs 7.7 months with radiation alone (HR, 0.53; P = .0001).

Survival also improved for the 189 patients who lacked MGMT promoter. Median overall survival was 10.0 months vs 7.9 months (HR for death, 0.75; P = .055; P = .08 for interaction).

Median progression-free survival was also improved for the combination therapy group: 5.3 months vs 3.9 months (HR for disease progression or death, 0.50; P < .001).

Quality of life was similar for both groups. As the authors expected, the rate of adverse events was slightly higher in the group that received combination therapy than in the patients who received to radiotherapy alone.

The study was supported by grants from the Canadian Cancer Society Research Institute, Schering-Plough (now Merck), and the EORTC Cancer Research Fund (Belgium). Dr Perry has stock and other ownership interests with DelMar Pharmaceuticals and VBL Therapeutic. Several coauthors have relationships with pharmaceutical companies, as detailed in the original article.

N Engl J Med. 2017;376:1027-37. Abstract

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