Biomarker Identifies Patients with Rare Brain Tumors Who Have a Survival Benefit from Chemotherapy Plus Radiation

June 2012, Vol 3, No 4

Chicago, IL—Patients with the relatively rare brain tumor anaplastic oligodendroglioma who were treated with adjuvant chemotherapy after standard radiation therapy had improved survival compared with radiation alone, especially if they had codeletion of chromosomes 1p/19q, according to long-term follow-up of the EORTC (European Organisation for Research and Treatment of Cancer) 2651 study reported at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO).

The difference in survival between the 2 arms was not evident when results were first reported in 2006, at a median of 5 years’ follow-up. But the curves for the 2 arms separated with longer follow-up, and at a median of ≥10 years of follow-up, patients with the codeletion of 1p/19q who received chemotherapy and radiation were 44% more likely to live longer than codeleted patients treated with radiation alone.

“We have identified a subgroup of patients who benefit from adjuvant chemotherapy following radiation,” said lead author Martin J. Van Den Bent, MD, Professor of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.

The study randomized 368 patients to radiotherapy and 185 to adjuvant chemotherapy with procarbazine, lomustine, and vincristine (PCV), which was considered the best option in 1995, when the study was first initiated. By the 2012 ASCO meeting, updated results were presented 17 years after the study was begun.

Median progression-free survival (PFS) and overall survival (OS) rates were significantly longer for the group treated with adjuvant PCV (P = .003 and P = .018, respectively); most of the benefit was driven by patients with the 1p/19q codeletion. (Patients were prospectively stratified for presence of this codeletion after other investigators showed that the codeletion was associated with greater sensitivity to chemotherapy and radiation.)

Looking at patients with the codeletion, PFS went from a median of 50 months with radiotherapy alone to 157 months for those who received adjuvant PCV (P = .002). Median OS was 112 months in the radiotherapy-alone arm, but median OS had not yet been reached in the adjuvant PCV plus radiotherapy arm.

These data are particularly impressive, because approximately 70% of patients originally assigned to radiotherapy alone crossed over to the adjuvant PCV arm at progression, which could underestimate the survival difference, Dr Van Den Bent commented.

A second study by Cairncross and colleagues reported at the meeting confirmed these results. The RTOG (Radiation Therapy Oncology Group) 9402 study showed that early PCV-chemotherapy-plus radiation improved survival in patients with anaplastic oligodendroglioma with the 1p/19q codeletion.

“These 2 studies, led by cooperative groups, define a new standard of care for 1p/19q-deleted anaplastic oligodendroglioma,” Dr Van Den Bent said.

These studies are practice-changing, according to Mark Gilbert, MD, M.D. Anderson Cancer Center, Houston, TX. Both studies established that a predictive biomarker informs treatment decisions. Dr Gilbert emphasized the importance of collecting tumor samples in clinical studies and archiving them for future analysis when new markers are identified.

“I commend the investigators for their perseverance and long-term follow-up,” Dr Gilbert said, noting that this led them to different conclusions from any initial results.

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