Adjuvant Temozolomide Improves Survival in Some Anaplastic Gliomas Patients

June 3, 2016

Adjuvant temozolomide chemotherapy following radiotherapy improves survival among patients with anaplastic gliomas that do not harbor 1p/19q co-deletions, according to interim results from a phase III trial.

[[{"type":"media","view_mode":"media_crop","fid":"49151","attributes":{"alt":"Martin J. van den Bent, MD, presenting data from the phase III CATNON Intergroup Trial on adjuvant temozolomide in glioma","class":"media-image","id":"media_crop_5591634747788","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5974","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","title":"Martin J. van den Bent, MD, presenting data from the phase III CATNON Intergroup Trial on adjuvant temozolomide in glioma","typeof":"foaf:Image"}}]]CHICAGO-Adjuvant temozolomide chemotherapy following radiotherapy improves survival among patients with anaplastic gliomas that do not harbor 1p/19q co-deletions, according to interim results from a phase III trial presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago (abstract LBA2000).

“These findings should expand treatment choices and change the way we treat patients with this rare form of brain cancer,” said coauthor Martin J. van den Bent, MD, a professor of neuro-oncology at Erasmus MC Cancer Center in Rotterdam, the Netherlands.

Patients whose anaplastic gliomas harbor co-deletions of chromosome arms 1p and 19q are known to respond better to chemotherapy and to survive longer. However, before the newly reported interim findings, it was not clear if patients whose tumors do not harbor these co-deletions, also benefitted from adjuvant chemotherapy with the oral drug temozolomide.

The phase III CATNON Intergroup Trial (EORTC 26053-22054) enrolled patients at 118 institutions in 12 countries between 2007 and 2015. The trial randomly assigned 748 patients to receive radiotherapy alone; radiotherapy plus concurrent temozolomide; radiotherapy and adjuvant temozolomide; and radiotherapy and concurrent temozolomide plus adjuvant temozolomide.

At a median follow-up of 27 months, a planned interim analysis revealed that adjuvant temozolomide following radiation (with or without concurrent temozolomide) was associated with delayed disease progression, compared to treatment regimens that did not include adjuvant temozolomide (progression-free survival [PFS], 42.8 months vs 19 months). For PFS, the authors reported a risk-adjusted HR of 0.586 (95% CI, 0.472–0.727; P < .0001).

Median overall survival has not yet been reached for the patients who received adjuvant temozolomide, but estimated 5-year overall survival rates for patients undergoing radiotherapy were 56% among those who also received adjuvant temozolomide, vs 44% for those who did not receive temozolomide (P = .003).

MGMT was methylated in 42% of patients for whom status could be assessed, and appeared to be associated with overall survival (HR, 0.54 [95% CI, 0.38–0.77]; P = .001), “but at this stage did not predict improved outcome to adjuvant [temozolomide],” Dr. van den Bent noted. Additional research will identify whether or not MGMT promoter methylation or IDH mutation (two prognostic mutations) affect the benefits of adjuvant temozolomide.

An international collaboration was essential to confirm the survival benefits of adjuvant temozolomide for these patients because this type of brain cancer is so rare. “It is very important to emphasize that this is a rare disease,” Dr. van den Bent noted. “It requires trials of many years’ duration to show improvements in outcome.”