New Standard of Care Emerges for Anaplastic Glioma Without 1p/19q Codeletion


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We were completely taken by surprise when we received the data.… These findings should expand treatment choices and change the way we treat patients with this rare form of brain cancer.
— Martin J. Van Den Bent, MD, PhD

Adjuvant temozolomide, after radiotherapy, improves overall survival in patients with grade 3 anaplastic glioma without 1p/19q codeletion, according to a phase III EORTC (European Organization for Research and Treatment of Cancer) study presented at the 2016 ASCO Annual Meeting.1 “We were completely taken by surprise when we received the data. At no point had we anticipated this outcome,” lead author Martin J. Van Den Bent, MD, PhD, Professor of Neuro-Oncology at Erasmus MC Cancer Center, Rotterdam, The Netherlands, commented at a press briefing.

The study showed a “huge difference” in survival—a 33% reduction in mortality risk—for patients receiving temozolomide in addition to radiotherapy, vs radiotherapy alone, he said. CATNON (EORTC 26053-22054) is the first randomized clinical trial to show that temozolomide improves overall survival in patients with grade II or III glioma, Dr. Van Den Bent revealed.

The CATNON data were released early, based on the positive findings observed at an interim analysis. The data provide the first evidence that temozolomide can benefit the subset of anaplastic glioma in patients without codeletion of chromosome arms 1p and 19q—a group previously known to be rather insensitive to chemotherapy, he said. “These findings should expand treatment choices and change the way we treat patients with this rare form of brain cancer,” he suggested.

Adjuvant Temozolomide in Glioma Subtype

  • Postradiotherapy temozolomide significantly improved overall survival in patients with grade 3 anaplastic glioma without the 1p/19a codeletion.
  • After a median follow-up of 27 months, median overall survival was 41.1 months in the radiotherapy-alone arm and had not been reached in the temozolomide arm; 5-year overall survival was 44% and 56%, respectively, representing a 33% reduction in risk (P = .003).

The study evaluated the use of temozolomide in patients without codeletion of chromosome arms 1p and 19q. Patients with this codeletion tend to respond to better to chemotherapy and have a better prognosis.

Study Details

The CATNON trial was conducted in 745 patients with grade 3 anaplastic glioma, none of whom had the 1p19q deletion. More than 1,400 patients were screened in 12 countries across 3 continents, and because the tumor is rare, enrollment took 8 years, Dr. Van Den Bent noted.

Following surgery and adjuvant radiation therapy, patients were randomized to receive no further treatment, temozolomide administered concurrently with radiation, 12 months of adjuvant temozolomide, or concurrent temozolomide plus an additional 12 months of adjuvant temozolomide. The primary endpoint was overall survival.

Interim analysis, after a median follow-up of 27 months, revealed median overall survival of 41.1 months for the radiotherapy-alone arm and it had not been reached by the arm receiving postradiotherapy adjuvant temozolomide. The independent data monitoring committee recommended early release of these data. The 5-year overall survival rates were 44% and 56%, respectively, representing a 33% reduction in risk (P = .003). Median progression-free survival was 43 months with adjuvant temozolomide and 19 months without it. The results of the concurrent part of the treatment remains unknown at present, as more follow-up is needed before conclusions can be drawn.

“Adjuvant temozolomide clearly improves survival,” Dr. Van Den Bent concluded. He said the use of adjuvant temozolomide is now “evidence-based medicine,” although questions remain over its concurrent use, which could increase long-term toxicity. ■

Disclosure: Dr. Van Den Bent has consulted for Merck, Roche, Celldex, Novocure, AbbVie, and Amgen; has received honoraria from Roche, Actelion, Celldex, Bristol-Myers Squibb, Merck, AbbVie, and Novocure; and has received research funding from AbbVie and Roche.

Reference

1. Van Den Bent MJ, et al: 2016 ASCO Annual Meeting. Abstract LBA2000. Presented June 5, 2016.


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