Allison Gandey
October 30, 2007 (Los Angeles) — Adding temozolomide (Temodar/Temodal, Schering-Plough) to radiotherapy extends the lives of many glioblastoma patients even longer than was once thought possible. Presenting here at the American Society for Therapeutic Radiation and Oncology (ASTRO) 49th Annual Meeting, investigators updated the results of their phase 3 randomized trial that explored the survival advantage of treatment.
«This is the good-news story of the meeting,» Anthony Zietman, MD, from Harvard Medical School in Boston, Massachusetts, and the education council chair for ASTRO, told reporters attending a news conference. «This is a very large European and Canadian trial, and it shows that we may actually be turning a corner in the treatment of glioblastoma. We finally have some evidence of long-term survivors.»
The landmark glioblastoma trial, first published in the New England Journal of Medicine (Stupp R et al. N Engl J Med. 2005; 352:987-996), showed an improvement in median and 2-year survival in patients receiving concomitant and adjuvant temozolomide with radiotherapy over those receiving radiotherapy alone.
Before this trial, there had reportedly been little progress in glioblastoma research over the previous 30 years. Patients typically lived between 6 and 12 months after diagnosis and there were almost no survivors beyond 2 years. Within months of publication, the addition of temozolomide to radiotherapy became the standard of care.
Eagerly Awaited Update Presented
These latest numbers, presented during a plenary session at ASTRO, show that the survival benefit of therapy can continue beyond 2 years for many patients. «The survival advantage conferred remains significant and clinically relevant with longer follow-up,» lead author René-Olivier Mirimanoff, MD, from the University Hospital Center and University of Lausanne, in Switzerland, told the meeting. «We have observed a significant proportion of patients surviving at least 4 years with this regimen,» he said.
He showed that 12% of patients receiving treatment lived for 4 years, compared with only 3% receiving radiation alone. A startling one-quarter of patients were still alive at 4 years — survival numbers never before seen in glioblastoma. However, Dr. Mirimanoff cautioned, the overall prognosis for most patients remains poor.
The investigators randomized 573 newly diagnosed patients to receive either standard radiotherapy (60 Gy in 30 daily fractions of 2 Gy, with a gross tumor volume–clinical target volume [GTV-CTV] margin of 2 to 3 cm) or the same radiotherapy with concomitant temozolomide (75 mg/m2 daily 7 days per week for 35 to 42 days), followed by up to 6 cycles of adjuvant temozolomide (150 to 200 mg/m2, daily for 5 days, every 28 days).
Overall Survival for Patients Receiving Therapy
Survival (y) Radiotherapy Alone (n=286), % Temozolomide Plus Radiotherapy (n=287), %
2 10.9 27.2
3 4.4 16.4
4 3.0 12.1
Hazard ratio, 0.63 (0.53 – 0.75); P < .0001
The investigators found that temozolomide added to radiotherapy was most effective in patients with the best prognostic factors. This was also the case for patients with methylated MGMT, a suppressed repair gene.
Speaking to reporters at a news conference, Dr. Mirimanoff emphasized that this regimen should remain the standard against which any new treatment modality or new combination is compared.
"This is the platform upon which we can add new agents in future research," Dr. Mirimanoff told Medscape Oncology. Among the trials in the works are initiatives looking at increasing doses of temozolomide and adding new targeted therapies and antiangiogenic agents.
This trial was supported by an unrestricted educational grant from Schering-Plough. Dr. Mirimanoff is a consultant and advisor for the company, as are a number of the other investigators on the study.
American Society for Therapeutic Radiation and Oncology 49th Annual Meeting: Plenary session 3. Presented October 29, 2007.