Zosia Chustecka

June 05, 2016

CHICAGO — Results were released early and are leading to talk about a new standard of care in glioma after an interim analysis showed a "huge difference" in survival between patients who received temozolomide in addition to radiotherapy, compared with those who received radiotherapy alone.

"It completely took us by surprise," said lead author Martin van den Bent, MD, professor of neuro-oncology at the Erasmus MC Cancer Center in Rotterdam, the Netherlands.

Previous trials in glioma have not shown any difference after 5 to 6 years after randomization, but in this study there was a significant difference even at 2 years, and at 5 years the difference was "huge," he said.

The findings come from the CATNON trial, conducted in 745 patients with grade 3 anaplastic glioma, all of whom did not have the 1p19q deletion, a genetic abnormality that is associated with better prognosis and chemosensitivity. In order to find the patients for this trial, more than 1400 patients were screened in 12 countries across three continents, and enrolment took 8 years, Dr van den Bent reported.

The results from the interim analysis, after a median follow-up of 27 months, show that 43% of patients treated with both temozolomide and radiotherapy were alive after 5 years, compared with 24% in the radiotherapy-alone group.

Put another way, the 5-year survival was 56% in those who received both temozolomide and radiotherapy, compared with 44% in those treated with radiotherapy alone (hazard ratio, 0.67; P = .003)

In this portion of the trial, temozolomide was administered after radiotherapy.

Dr Martin van den Bent

Two other groups in this trial are evaluating temozolomide given concurrently and temozolomide given both concurrently and after radiotherapy. "Further follow-up is required" to obtain answers on this, Dr van den Bent said. At the interim analysis, the efficacy boundary was not met, he said.

The required number of events for a full analysis of the results are likely not be collected until about 2024, which is when he will be retiring, Dr van den Bent joked.

"Adjuvant temozolomide clearly improves survival," Dr van den Bent concluded, and he also emphasized that this was the first randomized clinical trial to show an overall survival benefit in glioma.

In answer to a question from a clinician in the audience, who asked whether this was practice changing and how he should treat his glioma patients now, Dr van den Bent emphasized that the result for adjuvant temozolomide is clear, and that it should now be used together with radiotherapy in patients such as the participants in this trial. "That is now evidence-based medicine," he added. However, with the question remaining over concurrent temozolomide, he said that he remained hesitant, because it increases long-term toxicity.

Dr Brain Alexander

An American expert not involved in the trial agreed that it was practice changing. In fact, adjuvant temozolomide plus radiation will become a standard of care in glioma, commented Brain Michael Alexander, MD, PhD, disease center leader for radiation oncology at the Center for Neuro-Oncology, Dana-Farber Cancer Institute, and associate professor of radiation oncology at Harvard Medical School in Boston.

Temozolomide plus radiation is already a standard of care in glioblastoma multiforme, he noted, on the basis of phase 3 trial results reported in 2005 (N Engl J Med. 2005;352:987-996).

Many clinicians have extrapolated from this to also use the chemoradiation combination in glioma, he told Medscape Medical News, but this has not been supported by direct data until now.

New Standard of Care

Adjuvant temozolomide is a new standard for these patients, David Reardon, MD, clinical director at the Center for Neuro-Oncology, told the meeting in his discussion of the abstract.

He congratulated the researchers on their "truly labor-intensive efforts," and noted the significant difference in survival, with an increasing separation of the curves with time.

But he also added that the finding was "not too unexpected," as the addition of chemotherapy to radiotherapy improving survival is a "recurring theme in neuro-oncology."

In fact, a recently published study shows that the addition of the chemotherapy combination of procarbazine, lomustine, and vincristine to radiotherapy also prolonged survival in glioma (N Engl J Med. 2016;374:1344-1355).

Dr Reardon also noted that a question remains over the use of concurrent temozolomide in glioma, and he said he was looking forward to the final analysis from this trial, even if it takes until 2024.

Temozolomide was supplied free of charge by Schering-Plough/MSD. The study was funded by an unrestricted grant from Schering-Plough, and also grants from the European Organisation for Research and Treatment of Cancer (EORTC) and Cancer Research UK. Dr van den Bent reports a consulting or advisory role with Merck, Roche, Celldex, Novocure, AbbVie, Amgen; honoraria from Roche, Actelion, Celldex, Bristol-Myers Squibb, Merck, AbbVie, Novocure; and research funding from AbbVie and Roche. Dr Reardon reports honoraria from AbbVie, Bristol-Myers Squibb, Cavion, Celldex, Genentech/Roche, Inovio Pharmaceuticals, Juno Therapeutics, Merck, Midatech, Momenta Pharmaceuticals, Monteris Medical, Novartis, Novocure, Oxigene, Regeneron, Stemline Therapeutics; a consulting or advisory role with Bristol-Myers Squibb, Cavion, Celldex, Genentech/Roche, Inovio Pharmaceuticals, Juno Therapeutics, Merck, Midatech, Momenta Pharmaceuticals, Monteris Medical, Novartis, Novocure, Oxigene, Regeneron, and Stemline Therapeutics; and research funding from Celldex (Inst), Incyte (Inst), and Midatech (Inst).


American Society of Clinical Oncology (ASCO) 2016 Annual Meeting: Abstract LBA2000. Presented June 5, 2016.


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