In a brain cancer breakthrough, an international phase III clinical trial TROG 08.02 (GBM in elderly patients), which included Australian and New Zealand researchers and patients, has 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 (GBM), reducing the risk of death by 33%.

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.

Australian Trial Co-Chair and Radiation Oncologist, Dr Claire Phillips, said that in the past there had been a tendency to be ‘gentle’ when treating older patients with GBM because the prognosis was thought to be universally dismal and there was a reluctance to subject people to possible side-effects if they are only going to live for a short time.

“This study shows us that the prognosis is poor but perhaps not as bad as is generally believed. Importantly, it provides good evidence that older patients who have GBM, but who are otherwise quite healthy, benefit from moderately aggressive therapy without causing terrible toxicity. We (doctors, families and patients) can feel reassured that an older person will not be harmed by this treatment and will likely benefit from it,” Dr Phillips said.

University of Newcastle Conjoint Senior Lecturer Australian Trial Co-Chair and Radiation Oncologist, Dr Mike Fay, said this practice-changing study will help treat elderly patients with glioblastoma. “It’s a great example of international collaboration answering an important question in an uncommon tumour. It’s important to learn how to best use the cancer treatments we already have available. This study does this by shortening the radiotherapy course and adding temozolomide chemotherapy. It also shows the benefit of testing the tumour to predict the chance of response. In patients who have a specific genetic marker the benefit of temozolomide is significantly reduced.”

Lead study co-author 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, Canada said that although glioblastoma disproportionately affects older patients, there are no clear guidelines for treating these patients, and practice varies globally.

“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 (CCTG) with important collaboration from the European Organization for the Research and Treatment of Cancer (EORTC) and TROG Cancer Research (Trans-Tasman Radiation Oncology Group).

Investigators enrolled 562 patients 65 years and older who were newly diagnosed with glioblastoma, with 97 of these patients from Australia and New Zealand.

“TROG sites across Australia and New Zealand sites contributed 17% of the total world accrual to this study, which is well above the usual 10% that our population contributes to international studies. This reflects the strong commitment of TROG to improve the care and outcome of our patients,” Dr Phillips said.

“Cooperative trial group research conducted by such groups as TROG, the NCIC and the EORTC is a very important phenomenon in cancer research. Through team-work and collaboration it is possible to complete studies more quickly which means important treatment benefits get to the clinic more quickly.”

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 (40Gy in 15 fractions over 3 weeks) with concurrent and adjuvant temozolomide or radiation therapy alone.

Key Findings

Chemoradiation (treatment that combines chemotherapy with radiation therapy) 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.

“Although the difference in median survival seems modest, temozolomide significantly increased the chances of surviving two or three years. For an individual patient, that can mean being able to be part of another family holiday or celebration,” Dr Perry said. The one- year and two-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, a 47% reduction in the risk of death.

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.

About Gliobastoma

Glioblastoma is the most common primary brain cancer in adults and among the top five causes of death due to cancer. The disease kills an estimated 1,000 Australians each year. Glioblastoma occurs primarily in older people; the average age at diagnosis is 64 years.

News article courtesy of UON