CHICAGO—In the first study testing the use of both temozolomide and radiation in older adults with glioblastoma, side effects were slightly greater among patients receiving temozolomide, and overall quality of life was similar in both patient groups. The combination was also found to increase the survival period (Abstract LBA2).
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 Science Centres in Toronto, Canada, recently presented the data at the 2016 American Society of Clinical Oncology Annual Meeting. The international test was led by the Canadian Cancer Trials Group (CCTG). The European Organization for Research and Treatment of Cancer (EORTC) and the Trans-Tasman Radiation Oncology Group (TROG) collaborated with the CCTG on the trial.
In the randomized phase III trial, temozolomide (Temodar) chemotherapy was added during short-course radiation therapy. Monthly maintenance doses of temozolomide followed and significantly improved survival of elderly patients with glioblastoma. Risk of death was reduced by 33 percent.
The study enrolled 562 patients 65 years and older. All had been newly diagnosed with glioblastoma. The median patient age was 73 years and two-thirds were older than 70 years. Patients were randomly assigned to one of two categories: short course radiation therapy (40Gy in 15 fractions over 3 weeks) with concurrent and adjuvant temozolomide, or radiation therapy alone.
Findings showed that chemoradiation (treatment combining chemotherapy with radiation therapy) extended the median overall survival from 7.6 months with radiation therapy alone to 9.3 months. In addition, the combination slowed the tumor growth in the temozolomide group, with median progression-free survival of 5.3 months versus 3.9 months.
“Although the difference in median survival seems modest, temozolomide significantly increased the chances of surviving 2 or 3 years. For an individual patient, that can mean being able to be part of another family holiday or celebration,” said Perry.
The 1- and 2-year survival rates were 37.8 percent and 10.4 percent with radiation plus temozolomide versus 22.2 percent and 2.8 percent with radiation therapy alone.
For patients with a genetic abnormality, MGMT promoter methylation, the benefit of temozolomide was greater. For the subset of 165 patients, longer survival was found. The median overall survival was 13.5 months with temozolomide compared with 7.7 months of only radiation therapy. Also, patients treated with temozolomide had a 47 percent lower risk of death.
The study also analyzed quality of life. Standardized questionnaires EORTC QLQ-C30 and BN20 showed no difference in physical, cognitive, emotional, and social functioning between the two groups. More nausea, vomiting, and constipation were experienced by patients who received temozolomide than those who received radiation alone.
Glioblastoma, the most common primary brain tumor in adults, is among the top five causes of death due to cancer. The average age of diagnosis is 64 years. In the U.S., an estimated 12,120 people will be diagnosed with the disease this year according to the American Brain Tumor Association.
“Glioblastoma is frequently diagnosed in older individuals, and these are important data showing that our best therapies can work and be tolerable for elderly patients,” said Brian Alexander, MD, MPH, ASCO expert in brain cancers. “It's good to have an option to offer patients that we know can have a positive impact, though still physicians and their patients need to weigh the benefits of this approach carefully.”
“I think this is really important in that we are testing in the population that actually gets the disease, the older population,” emphasized ASCO President Julie M. Vose, MD, MBA, FASCO, of University of Nebraska Medical Center in Omaha, who served as the plenary briefing moderator. “It's very important that we target the population that (is affected).”
“Although glioblastoma disproportionately affects older patients, there are no clear guidelines for treating these patients, and practice varies globally,” concluded Perry. “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.”
Romi Herron-Cologna is a contributing writer.