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ASCO 2016: Temozolomide Chemotherapy Plus Short-Course Radiotherapy Improves Survival in Elderly Patients With Glioblastoma

Key Points

  • Chemoradiation extended the median overall survival from 7.6 months with radiation therapy alone to 9.3 months. In addition, tumor growth was slower in the temozolomide group, with median progression-free survival of 5.3 months vs 3.9 months.
  • The 1-year and 2-year survival rates were 37.8% and 10.4% with radiation plus temozolomide vs 22.2% and 2.8% with radiation therapy alone.
  • In a subset of patients with MGMT promoter methylation, the median overall survival was 13.5 months with temozolomide and 7.7 months with radiation therapy alone. Patients who received temozolomide had a 47% lower risk of death than those who received radiation therapy alone.

A Canadian-led randomized phase III trial found that adding temozolomide chemotherapy during short-course radiation therapy, followed by monthly maintenance doses of temozolomide, significantly improved survival of elderly patients with glioblastoma, reducing the risk of death by 33%.

These data were presented by Perry et al in ASCO’s Plenary Session as part of the 2016 ASCO Annual Meeting (Abstract LBA2).

This is the first study to test the combination of temozolomide and radiation therapy in older adults, who account for half of all patients with this disease. While side effects were slightly greater among patients receiving temozolomide, overall quality of life was similar in both patient groups.

“Although glioblastoma disproportionately affects older patients, there are no clear guidelines for treating these patients, and practice varies globally,” said lead study coauthor James R. Perry, MD, FRCPC, The Crolla Family Endowed Chair in Brain Tumour Research at the Odette Cancer and Sunnybrook Health Sciences Centres in Toronto. “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.”

About the Study

This international phase III trial was led by the Canadian Cancer Trials Group with collaboration from the European Organisation for Research and Treatment of Cancer (EORTC) and the Trans-Tasmin Radiation Oncology Group.

Investigators enrolled 562 patients 65 years and older who were newly diagnosed with glioblastoma. The median patient age was 73 years, and two-thirds were older than 70 years. The patients were randomly assigned to either short-course radiation therapy (40 Gy in 15 fractions over 3 weeks) with concurrent and adjuvant temozolomide or radiation therapy alone.

Key Findings

Chemoradiation extended the median overall survival from 7.6 months with radiation therapy alone to 9.3 months. In addition, tumor growth was slower in the temozolomide group, with median progression-free survival of 5.3 vs 3.9 months.

“Although the difference in median survival seems modest, temozolomide significantly increased the chances of surviving 2 or 3 years,” said Dr. Perry. The 1-year and 2-year survival rates were 37.8% and 10.4% with radiation plus temozolomide vs 22.2% and 2.8% with radiation therapy alone.

The benefit of temozolomide was greater among 165 patients with MGMT promoter methylation, a genetic abnormality linked to better response to chemotherapy and longer survival in this disease. In this subset of patients, the median overall survival was 13.5 months with temozolomide and 7.7 months with radiation therapy alone. Patients who received temozolomide had a 47% lower risk of death than those who received radiation therapy alone.

Quality-of-life analyses using standardized questionnaires EORTC QLQ-C30 and BN20 showed no differences in physical, cognitive, emotional, and social functioning between the two groups. However, patients who received temozolomide had more nausea, vomiting, and constipation than those who received radiation therapy alone.

This study received funding from the Canadian Cancer Society Research Institute and by an unrestricted grant from Schering-Plough/Merck Inc.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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