Chemoradiation Boosts Glioblastoma Survival in Real-World Setting

Neil Osterweil

October 13, 2020

A comparison of U.S. and European treatment patterns for glioblastomas provides further evidence that adding systemic chemotherapy with temozolomide to radiotherapy offers a significant survival benefit over radiotherapy alone, and wider uptake of chemoradiation in Europe would extend the benefit to more patients.

That conclusion comes from a study of registry data from both sides of the Atlantic. The study showed a doubling in 2-year survival rates for patients with glioblastomas treated with radiotherapy plus chemotherapy compared with radiotherapy alone, a practice change that was prompted by a phase 3 trial published in The New England Journal of Medicine in 2005.

"Using population data from cancer registries, we observed a huge increase in radiotherapy plus chemotherapy between 1999 and 2013 in Europe and the U.S.," said Francesco Giusti, PhD, of the European Commission Joint Research Center in Ispra, Italy.

"Data from 1999 to 2005 was already showing a clear survival advantage for patients treated with chemotherapy plus radiotherapy compared with radiotherapy alone," he added.

However, when Giusti and colleagues compared practice patterns from before and after the publication of the practice-changing trial, they found that about 10% more patients in the United States were receiving combined chemotherapy and radiation, a difference reflected in superior survival rates in the U.S., he said.

Giusti presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

He and his colleagues looked at data from cancer registries contributing to the European Cancer Information System and the U.S. National Cancer Institute's Surveillance Epidemiology and End Results data.

The data set included patients diagnosed from 1999 through 2013 with glioblastoma as a first tumor.

During that time, results from the aforementioned phase 3 trial were published. They showed that, at a median follow-up of 28 months, the median survival was 14.6 months for the 287 patients assigned to radiotherapy plus temozolomide, compared with 12.1 months for the 286 patients randomized to radiotherapy alone.

The unadjusted hazard ratio for death in the combination therapy group was 0.63 (P < .001). The 2-year survival rate was 26.5% for chemoradiation and 10.4% for radiation alone.

Adding temozolomide to radiotherapy in the trial also appeared to be safe. The incidence of grade 3 or 4 hematologic adverse events was 7%.

Registry Data Study

To see how practice patterns changed in the United States and Europe after publication of the trial, Giusti and colleagues used registry data to calculate the proportion of cases by treatment type and overall survival during 1999-2005 (pre-study) and 2009-2013 (post-study).

The data included 34,229 cases from 11 countries in Europe and 36,925 cases from the United States.

The percentage of patients receiving both chemotherapy and radiation increased steadily over the study period. For example, among 18- to 49-year-olds, the percentage receiving the combined modalities in Europe increased from 20% in 1999-2001 to 70% in 2010-2013. In the United States, 40% of the same age group received combination therapy in 1999-2001, and this percentage grew to 80% in 2010-2013.

Overall survival rates in the general population were similar to those seen in the clinical trial during 1999-2005, when 2-year overall survival rates for patients treated with radiation alone were 11% in Europe and 12% in the United States. For patients treated with combined therapy, the respective 2-year survival rates in Europe and the United States were 24% and 25%.

"In the period after the trial, we observed a increasing 2-year survival rate to 28% in Europe and 29% in the U.S. for patients with radiotherapy plus chemotherapy," Giusti said.

Real-World Results

Invited discussant Matthias Preusser, MD, of the Medical University of Vienna in Austria, said the study shows that "population-based investigations are very valuable and should be further developed so that we can see how treatment patterns vary between countries and what the regional variations are, and whether new treatment standards actually reach clinical practice, and also to see whether there's an effect on a population basis that is different from what is seen in controlled clinical trials."

Preusser said it's clear from the study that survival is increased with the addition of chemotherapy to radiotherapy, and more patients in the United States than in Europe received the combination during the study period.

Pointing to a treatment algorithm from the European Association of Neuro-oncology published in 2017, Preusser noted that radiotherapy alone may still be recommended for patients with unfavorable prognostic factors or patients 70 years and older with methylguanine-DNA methyltransferase promoter non-methylated tumors.

"It seems the differences in the age distribution between the U.S. and European populations that were analyzed could be one explanation why the radiochemotherapy combination was applied more often in the U.S. population," Preusser said.

No outside funding was used to support the study. Giusti and coauthors reported having no conflicts of interest. Preusser disclosed relationships with multiple companies, including Merck, which markets temozolomide under the name Temodar.

SOURCE: Giusti F et al. ESMO 2020. Abstract 365MO.

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