In univariate analysis 1p/19q co-deletions, IDH, and MGMT were all independent prognostic factors for survival (P less than .0001), with only MGMT falling out in multivariate analysis.
Virtually all 1p/19q co-deleted tumors show IDH mutation and virtually all IDH-mutated tumors show MGMT promoter methylation, Dr. van den Bent pointed out. Post-hoc testing revealed IDH mutations in 46% of 178 patients and MGMT methylation in 74% of 183 patients tested.
In a separate presentation at the meeting, North American investigators reported that patients with 1p/19q co-deletions lived twice as long or 14.7 years with PCV chemotherapy followed by radiation, compared with 7.3 years with radiation alone in the phase III, 291-patient Radiation Therapy Oncology Group (RTOG) 9402 trial (HR 0.59; P = .03).
Survival times were not significantly different at 2.6 years and 2.7 years, respectively, in patients without such deletions (HR 0.86; P = .39).
In all, 64% of patients given PCV experienced grade III-IV toxicity, although salvage treatment was more common with radiation only (81% vs. 57%; P = .04).
The overall survival benefit was observed after a median follow-up of 11.3 years, reversing an early analysis in 2006 that showed no overall survival benefit for the combined therapy, according to lead author Dr. J. Gregory Cairncross, professor and head of clinical neurosciences at University of Calgary (Alta.).
Dr. Bruce J. Roth
The same phenomenon was reported in the EORTC cohort.
"It could be because, after 6 or 7 years, the effects of radiation therapy begin to wear off and then the beneficial effects of chemotherapy kick in," Dr. van den Bent speculated. "We don’t know. It’s a unique phenomenon. I can’t recall having seen this before, but we have two trials showing exactly the same separation of the survival curves after only 6 years."
Press conference moderator Dr. Bruce J. Roth, an oncology professor at Washington University in St. Louis, said most AOD patients in the United States are treated with radiation after surgery, and that the minority of those who do receive chemotherapy will likely continue to receive temozolomide because of the ease of administration and lower toxicity.
Dr. van den Bent said the ongoing intergroup phase III CATNON trial of concurrent and adjuvant temozolomide in patients with non-1p/19q co-deleted tumors should further define which patients benefit from chemotherapy, but that results will not be available for many years.
Dr. Van den Bent reports consulting with and honoraria from MSD. A co-author reports consulting with MSD and honoraria from GlaxoSmithKline and Roche Diagnostics.
RTOG 9402 was supported by grants from the National Cancer Institute, North Central Cancer Treatment Group, Southwest Oncology Group, Eastern Cooperative Oncology Group and the NCIC Clinical Trials Group.
* This story has been updated and revised on 6/8/2012.