(CHICAGO, IL) – Patients with anaplastic oligodendroglioma with co-deletion for chromosomes 1p and 19q survive significantly longer after receiving PCV (procarbazine, lomustine and vincristine) chemotherapy immediately prior to radiotherapy compared with radiotherapy alone, according to long-term follow-up of a randomized phase 3 study presented at the 2012 American Society of Clinical Oncology Annual Meeting.
Initial results from the RTOG 9402 study were published in 2006; however, at that time, death had occurred in <50% of patients with 1p/19q co-deleted tumors and molecular information was missing on 30% in the trial, said J. Gregory Cairncross, MD, of the University of Calgary, Calgary, AB, Canada. He presented median follow-up data of 11.3 years (18 years after the first patient was randomized); 1p/19q data were available on 90% of participants.
The study randomized 291 patients to either PCV+RT (n=148) or RT alone (n=143). No difference in median overall survival (OS) was observed between the two arms: PCV+RT was 4.6 years vs RT alone, 4.7 years (HR=0.79; P=0.1). Adjusted survival analysis using a step-wise hazards model that included age at diagnosis, steroid use, number of lesions, neurological function, KPS, type of surgery, pure vs mixed histology, degrees of anaplasia, treatment assignment and co-deletion status resulted in a statistically significant OS (HR=0.67; P=0.01); however, Dr. Cairncross cautioned that this conclusion is from an unplanned analysis.
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Patients with 1p/19q co-deleted tumors lived much longer after PCV+RT (n=59; 14.7 years) compared with those who received only radiotherapy (n=67; 7.3 years; HR=0.59; P=0.03). For the non-co-deleted cases, median OS was 2.6 years in the PCV+RT arm (n=76) and 2.7 years in the RT alone arm (n=61)(HR=0.85; P=0.39). Although no difference in median OS was observed among patients with 1p deletion only, 19q deletion only, or neither deleted, those with isolated 19q deletion lived longer, he said.
“In this setting, 1p/19q co-deletion was both prognostic and predictive, and the early PFS benefit in co-deleted cases was a harbinger of their longer OS,” Dr. Cairncross said. He added that forthcoming analysis of cognitive function and quality of life “could modify our view of PCV+RT, and data on late toxicity is sparse.” Based on these results, the standard arm in the NCCTG-led co-deletion trial is being revisited.
