Anaplastic Oligodendrogliomas

ImageCHICAGO—A new marker appears to identify patients with anaplastic oligodendroglioma who will respond to radiotherapy and adjuvant chemotherapy. Data from the European Organization for Research and Treatment of Cancer (EORTC) 26951 study, reported here at the American Society of Clinical Oncology Annual Meeting, show dramatic increases in progression-free and overall survival in patients with the 1p/19q co-deletion treated with radiotherapy followed immediately by PCV chemotherapy—i.e., procarbazine, CCNU (lomustine), and vincristine (Abstract 2). The marker was both prognostic and predictive, the investigators reported in presenting the study at the Plenary Session. Interestingly, although in earlier reports there was no significant benefit to any patients with adjuvant PCV at 60 months follow-up, this new report comes after follow-up of 140 months. The latest report shows that benefits have been greatest in patients with a 1p/19q co-deletion, which may be a valuable marker to direct management for these patients in the future. “The 1p/19q status in anaplastic oligodendroglioma provides a better understanding of which patients will benefit from chemotherapy immediately following radiotherapy,” said the study's lead author, Martin J. van den Bent, MD, Professor in the Neuro-Oncology Unit at Daniel den Hoed Cancer Center/Erasmus University Medical Center in The Netherlands. The trial began with an enrollment of 368 patients, 183 receiving radiotherapy alone and 185 receiving adjuvant PCV immediately following radiotherapy. At 140 months, 298 patients (81%) had disease progression and 87 patients (25%) were still alive. Patients who received adjuvant PCV had a median overall survival of 42 months, compared with 31 months for those receiving radiotherapy alone. The hazard ratio was 0.75 in the intent-to-treat population. The median progression-free survival time was 24 months with adjuvant chemotherapy after radiotherapy vs. 13 months without, with a hazard ratio of 0.66, he reported. Molecular Subgroup Identified “We then asked ourselves if we were able to identify particular molecular subgroups that benefitted more from the addition of PCV chemotherapy,” he said. A preplanned analysis of 80 patients with deletion of both the 1p and 19q arms of the respective chromosomes showed a much greater difference in survivals. Overall survival for the 43 patients with co-deletions receiving adjuvant chemotherapy has not been reached, he said, while overall survival for the 37 patients with co-deletions treated with radiotherapy alone was 112 months. That hazard ratio was 0.56. Progression-free survival for co-deletion patients was 157 months with adjuvant therapy vs. 50 months for radiotherapy alone, with a hazard ration of 0.42. For comparison, overall survival for the 114 patients receiving adjuvant chemotherapy who did not have co-deletions was 25 months vs. 21 months for the 122 patients receiving radiotherapy alone who did not have co-deletions, with a hazard ratio for overall survival of 0.83.MARTIN J. VAN DEN BENT, MD: “The 1p/19q status in anaplastic oligodendroglioma provides a better understanding of which patients will benefit from chemotherapy immediately following radiotherapy.”Progression-free survival for non-co-deletion patients was 15 months with PCV and nine months for radiotherapy alone, with a hazard ration of 0.73. Earlier Report Differed A report on this trial in 2006, at a median of 60 months follow-up, showed that adjuvant PCV chemotherapy improved progression-free survival but that overall survival outcomes were similar whether PCV was given immediately following radiotherapy or at the time of recurrence. Van den Bent said the latest EORTC 26951 findings are confirmed by a Radiation Therapy and Oncology Group study (RTOG 9402), led by J. Gregory Cairncross, MD, Professor and Head of the Department of Clinical Neurosciences at the University of Calgary, and reported here during an oral abstract session. That trial showed the same benefit of early PCV chemotherapy compared with initial radiotherapy alone (Abstract 2008b). “His findings are exactly the same as the findings we are presenting today,” said van den Bent. “Together, these studies make the new standard of care for 1p/19q-codeleted anaplastic oligodendroglioma.” The question now is what to do with non-deleted tumors. “At this point in time we cannot draw definitive conclusions,” he said, adding that trials under way with temozolamide chemotherapy in patients with grade 3 tumors may provide an answer. Discussant: Radiation Alone No Longer Adequate for These Patients The study's Discussant, Mark R. Gilbert, MD, Professor of Cancer Research in the Department of Neuro-Oncology at the University of Texas MD Anderson Cancer Center, said the two studies had “practice-changing results.” “Radiation therapy alone is no longer adequate for patients with anaplastic oligodendroglioma with 1p/19q co-deletion,” he said. “Existing data support first-line treatment with radiation and chemotherapy.”Speaking of this study and the related earlier RTOG 9402 trial, Discussant MARK R. GILBERT, MD, said, “Both establish a predictive molecular marker that informs treatment decisions. The results re-emphasize the need to consider anaplastic oligodendroglioma as two distinct entities based on 1p/19q status.”Gilbert compared EORTC 26951 and RTOG 9402 and said they showed remarkably similar data in patients with 1p/19q co-deletions in anaplastic oligodendroglioma. “Both studies establish a predictive molecular marker that informs treatment decisions. The results re-emphasize the need to consider anaplastic oligodendroglioma as two distinct entities based on 1p/19q status.” Importance of Collecting Tumor Samples in Clinical Studies The perseverance of the researchers in the long-term follow-up provided very different conclusions from initial observations, he added. “The statistical endpoint was achieved only after sufficient time and major effort to increase tumor tissue acquisition. 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, he noted. “Collecting and archiving tumor samples allows for reassessing clinical outcomes when new markers are discovered.”

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