Lengthy-term outcomes from the CATNON trial confirmed that
In an interview with CURE, Dr. Martin J. van den Bent, a neuro-oncologist at Erasmus MC Most cancers Heart in Rotterdam, and the lead investigator of the trial, stated the profit was seen with 12 cycles of adjuvant temozolomide given after radiation, not with temozolomide given concurrently throughout radiation, which didn’t enhance outcomes and should add toxicity.
He emphasised that molecular testing, together with IDH standing, is vital to information remedy choices, famous that sufferers with IDH-wild kind tumors didn’t profit and highlighted ongoing efforts to cut back long-term cognitive uncomfortable side effects whereas exploring new methods akin to IDH inhibitors and approaches that will safely delay radiation or chemotherapy.
CURE: For sufferers with newly recognized IDH-mutant anaplastic astrocytoma, what’s an important takeaway from the long-term CATNON trial outcomes?
van den Bent: What we discovered is that if we add 12 cycles of adjuvant temozolomide to radiation remedy, 59.4 grey given in 33 fractions, we considerably enhance outcomes for these sufferers.
The examine confirmed a transparent survival profit with adjuvant temozolomide, however not with concurrent temozolomide. How ought to sufferers perceive that distinction when discussing remedy plans with their care crew?
There are two methods of administering temozolomide in newly recognized glioma sufferers. You may give it throughout radiation remedy each day. Radiation remedy normally lasts about six weeks, and sufferers obtain temozolomide day by day at a decrease dose.
Then there are the adjuvant cycles, by which temozolomide is given on the primary 5 days of each 28-day cycle, so 5 days on and 23 days off.
What we confirmed within the CATNON trial is that the concurrent a part of the temozolomide routine didn’t impression outcomes. Since now we have considerations about including toxicity to radiation remedy, we really feel that concurrent temozolomide shouldn’t be given in these sufferers, in contrast to in grade 4 glioblastoma sufferers.
The median total survival with adjuvant temozolomide prolonged past 12 years in sufferers with IDH-mutant tumors. What does this size of follow-up inform us in regards to the sturdiness of profit?
It reveals that, in contrast with radiation remedy alone, the place median survival was between 5 and 6 years, there’s a important proportion of sufferers who dwell for a really very long time.
We now have some concepts about who these sufferers are. Usually, they’re sufferers with out different mutations aside from the IDH mutation, so there’s a genetic background to that. We additionally assume, based mostly on different research, that sufferers who’ve extra in depth main resections do higher. Surgical procedure is a crucial a part of remedy. We didn’t particularly examine that within the CATNON trial, however different research help that discovering.
The trial discovered no profit from temozolomide in sufferers with IDH-wild kind tumors. How do these findings reinforce the function of molecular testing at prognosis?
Molecular testing at prognosis is now commonplace of care in all Western nations as a result of the prognosis is constructed on the presence or absence of those mutations.
If an grownup has a diffuse glioma, the tumor is robotically examined for an IDH mutation as a result of that guides the diagnostic course of. That data must be accessible in all sufferers present process surgical procedure. Then this trial tells us what the optimum remedy after surgical procedure must be.
A number of molecular options have been linked to worse outcomes however didn’t predict profit from temozolomide. How may these insights form future analysis or remedy approaches?
With this trial, now we have basically accomplished many of the medical analysis that may be carried out in optimizing radiation remedy and chemotherapy for these sufferers. We now have performed many trials over the previous 20 to 30 years, and this examine form of concludes that effort.
If we wish to additional enhance outcomes, now we have to look in different instructions. IDH inhibitors and different lessons of brokers are examples. We want new methods.
We additionally acknowledge that though radiation remedy and chemotherapy enhance total survival, there are uncomfortable side effects. Many sufferers, years later, expertise cognitive deficits, issues with focus, reminiscence impairment and fatigue. These are long-term hostile results we see after radiation remedy.
Our present efforts concentrate on methods to cut back these uncomfortable side effects, akin to suspending radiation remedy and chemotherapy and exploring different therapies first. These alternate options nonetheless must be recognized for grade 3 tumors.
What message do you have got for sufferers who’re dealing with this illness?
If you happen to don’t deal with this tumor appropriately, it’s aggressive. With radiation remedy alone, median survival was solely 5 to 6 years. Including chemotherapy to radiation remedy clearly improves outcomes, and that’s an vital message.
Now we’re making an attempt to enhance outcomes additional. A number of trials are ongoing, including IDH inhibitors to upkeep remedy or exploring whether or not different therapies will be given earlier than radiation and chemotherapy.
We’re additionally asking whether or not we are able to enhance high quality of survival by suspending radiation remedy and chemotherapy with different approaches. However that is nonetheless largely unexplored territory, and we’d like new methods.
Reference
- “Concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC examine 26053-22054): closing and exploratory analyses of a randomised, open-label, section 3 trial” by Prof Martin J van den Bent, et al., The Lancet Oncology.
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