Long-term CATNON trial results show radiotherapy followed by adjuvant temozolomide extends survival in patients with newly diagnosed anaplastic glioma.
New research from the international CATNON trial shows that patients with newly diagnosed 1p/19q non-co-deleted anaplastic astrocytomas who received radiotherapy followed by adjuvant temozolomide lived significantly longer than those who did not, according to study results published in The Lancet Oncology by lead study author Dr. Martin J. van den Bent and colleagues.
CURE sat down with van den Bent, neuro-oncologist of Erasmus MC Cancer Center in Rotterdam, to further discuss the study results and its implications for patients.
“Adding chemotherapy to radiation therapy really improves the outcome in patients [with newly diagnosed 1p/19q non-co-deleted anaplastic astrocytomas],” said van den Bent. “That's an important message. What we have to do [now] is try to further improve outcomes, and there are several trials now ongoing.”
Overall survival (OS): time from the start of treatment until death from any cause.
IDH mutation: a genetic change in the isocitrate dehydrogenase gene that can affect tumor behavior and response to treatment.
1p/19q non-co-deleted: a tumor characteristic where specific chromosome regions (1p and 19q) are not deleted, which influences prognosis and response to therapy.
In the long-term follow-up, 751 participants were randomly assigned to one of four treatment groups: radiotherapy alone, radiotherapy with concurrent temozolomide, radiotherapy with adjuvant temozolomide or radiotherapy with both concurrent and adjuvant temozolomide. Of these, 444 participants had tumors with an isocitrate dehydrogenase (IDH) mutation.
“There are two ways of administering temozolomide in newly diagnosed glioma patients,” said van den Bent during the interview. “You can give it during radiation therapy on a daily basis (concurrent)... And then there are adjuvant cycles in which temozolomide is given to patients on the first five days of every in cycles of 28 days. Five days on [and] 23 days off”
Results showed that adjuvant temozolomide given after radiotherapy improved overall survival in the entire intention-to-treat population. The hazard ratio was 0.65, indicating a 35% reduction in the risk of death compared with patients who did not receive adjuvant therapy. Concurrent temozolomide given during radiotherapy, however, did not significantly affect overall survival.
Among patients with IDH-mutated tumors, median overall survival was 12.5 years for those who received adjuvant temozolomide, compared with six years for those who did not. Concurrent temozolomide alone did not produce a statistically significant survival benefit, with a median of 9.7 years versus 7.2 years without concurrent therapy. No survival benefit was observed in patients with IDH wild-type tumors.
Genetic subtypes and other DNA alterations, including PDGFRA and CDK4 amplification, homozygous deletion of CDKN2A and total copy number variation, were linked to poorer outcomes, but none predicted whether patients would benefit from temozolomide.
The CATNON study, conducted between December 2007 and September 2015 at 137 institutions across Australia, Europe and North America, followed participants for a median of nearly 11 years.
Radiotherapy was delivered at a total dose of 59.4 Gy in 33 fractions. Concurrent temozolomide was given at 75 milligrams per square meter (mg/m2) per day during radiotherapy. Adjuvant temozolomide was administered in 12 cycles, with doses of 150 to 200 mg/m2 on days 1 to 5 of each 28-day cycle. The study was open-label and phase 3, and its primary endpoint was overall survival.
A press release noted that safety data had been published previously. No new safety information was included in the long-term follow-up report.
“Although we all realize that giving radiation therapy and chemotherapy after surgery improves the overall survival,” van den Bent said during the interview, “we all realize that there is a side effect of this, because many of these patients in some point in time will start to complain about what we call cognitive deficits, issues with concentration, issues with memory impairment [and] fatigue. These are all [side effects] that we see happen in patients many years after the radiation therapy. Our efforts are to develop strategies that help us to avoid the side effects by trying to postpone radiation therapy and chemotherapy only for other treatments.”
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