AOD Predictive Marker Established by Complementary Studies

A long-term follow-up of th e European Organisation for Research and Treatment of Cancer (EORTC) 26951 study reported at the Plenary Session on Sunday showed that patients with anaplastic oligodendroglioma (AOD) who received chemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) immediately following radiation therapy (RT) were 44% more likely to live longer if their tumors showed a deletion of both the 1p and 19q arms of the respective chromosomes compared with patients receiving RT alone following disease progression (Abstract 2).

Martin J. van den Bent, MD, of Erasmus University Medical Center and Daniel den Hoed Cancer Center, Netherlands, said, “Now we have identifi ed a subgroup of patients who benefit from adjuvant chemotherapy following RT.” These data, with a median follow-up of 140 months, are in contrast to those initially reported in 2006 (with a median of 60 months follow-up) that survival benefits for patients were similar if PCV was administered immediately following RT or at the time of recurrence.

Of the 368 patients initially enrolled in the study, 183 patients received RT and 185 received adjuvant PCV immediately following RT. At the time of this analysis, 281 patients had died. Although median progression-free survival (PFS) and overall survival were significantly longer for patients receiving RT and adjuvant PCV (p = 0.003 and p = 0.018, respectively), of note were the clinical benefits reported for patients with AOD with the 1p/19q codeletion. In this prospectively defined patient population, PFS was 50 months if patients received RT alone and 157 months if they received PVC following RT (HR = 0.42, 95% CI: 0.24–0.74; p = 0.002). In addition, median survival was 9 years for patients receiving RT alone and was not yet reached after 12 years for patients receiving PVC immediately following RT (HR = 0.56, 95% CI: 0.31–1.03; p = 0.059). Dr. van den Bent told ASCO Daily News, “These data are impressive given that there was at least 70% of cross-over from patients in the RT arm of the study.”

Dr. van den Bent suggested that the 1p/19q status of these tumors provides a better understanding of which patients with AOD will benefi t from chemotherapy immediately following RT. A similar Radiation Therapy and Oncology Group study (RTOG 9402), led by J. Gregory Cairncross, MD, of the University of Calgary, Canada, and reported at Sunday’s Central Nervous System Tumors Oral Abstract Session, shows the same benefi t of early PCV chemotherapy as opposed to initial RT alone (Abstract 2008b). “Taken together, these studies define the new standard of care for 1p/19q-codeleted AOD,” Dr. van den Bent said.

Discussant Mark R. Gilbert, MD, of the University of Texas M. D. Anderson Cancer Center, called the two studies “practice changing.” He compared EORTC 26951 and RTOG 9402 and showed the remarkable similarity in data in patients with 1p/19q-codeleted AOD. “The upfront combination of RT and PCV demonstrated improved survival in patients with AOD with 1p/19q codeletion,” he said. He regarded both studies as establishing a predictive molecular marker that informs treatment decisions and remarked on the perseverance of the long-term followup that provided very different conclusions from initial observations.

“The importance of collecting tumor samples in clinical studies cannot be overemphasized. When these studies were undertaken, the molecular marker that predicted treatment benefit had not yet been discovered. Collecting and archiving tumor samples allows for reassessing clinical outcomes when new markers are discovered,” Dr. Gilbert concluded.