Chemo+radio combo for glioblastoma

9 Mar 2009

Addition of chemotherapy to radiotherapy continues to increase survival in patients with brain tumours for up to 5 years

Giving patients with glioblastoma—the most common and aggressive form of primary brain tumour—the chemotherapy drug temozolomide in combination with radiotherapy increases their survival compared with those receiving radiotherapy alone and this improvement persists for up to 5 years, according to the final results of the EORTC-NCIC trial, published in the May edition of The Lancet Oncology.

For over 30 years, post-operative radiotherapy was the standard treatment for glioblastoma, but offered only modest survival benefits to patients. The average life-expectancy of patients with glioblastoma was 9–12 months.

In 2004, after many disappointing attempts with drug therapy, the large international phase III EORTC-NCIC trial finally showed some promising results in this difficult setting where use of combined treatment with radiotherapy and temozolomide reduced the risk of dying from glioblastoma by 37% (HR for death 0.63, CI 0.53–0.75) compared with radiotherapy alone. At 2 years, 27% of patients receiving temozolomide in combination with radiotherapy (TMZ/RT) were alive, compared with just 10% of patients being treated with radiotherapy (RT) alone. However, whether this survival benefit would persist over time was unknown.

In this study, Roger Stupp and colleagues report the long-term 5-year outcomes of patients involved in the original EORTC-NCIC trial. The authors also examined whether clinical factors and the molecular profile of the tumours would identify patients with particularly good survival or response to chemotherapy.

Findings showed that at 3 years, 16% of patients receiving TMZ/RT were alive compared with only 4% of patients having RT alone. At 4 years, overall survival data after combined treatment were 12.1% compared with 3% for RT alone and at 5 years, 9.8% vs 1.9%, respectively. Importantly, improvement in survival was seen across all clinical prognostic subgroups, even in patients considered to have a poor diagnosis—such as more elderly patients or patients whose tumour could not be removed.

In exploratory analyses, overall survival data were best in patients being treated with TMZ/RT whose tumours carried an inactivated MGMT gene (0-6-methylguanine-DNA methyltransferase). Almost half of these patients were alive after 2 years and they also showed a persistent survival advantage at 3, 4, and 5 years. The authors suggest that testing tumours for the methylation status of the MGMT gene would allow the selection of patients most likely to benefit from this treatment.

Despite this improvement—with a substantial proportion of patients surviving for several years after treatment with TMZ/RT—most still died. The authors noted no difference in the pattern of recurrence between patients treated with RT alone or TMZ/RT, and caution that upfront combined therapy may be effective in reducing tumour bulk and aggressiveness, but it does not truly modify the natural behaviour of the disease, and thus is unlikely to lead to a cure.