Restarting Selumetinib Promising for Recurrent Low-Grade Glioma in Kids

At the International Symposium on Pediatric Neuro-Oncology (ISPNO), investigators reported prospective evidence supporting retreatment with the MEK inhibitor selumetinib (Koselugo) in children with recurrent low-grade glioma.

In this MedPage Today video, Jason Fangusaro, MD, of Emory University School of Medicine in Atlanta, discusses the findings and why they offer compelling evidence as to why retreatment should be considered for patients who benefitted from initial treatment.

Following is a transcript of his remarks:

The study was a large study of a drug called selumetinib, which is a MEK inhibitor which has been tested for many, many years in pediatric low-grade glioma. And the original study called PBTC-029 led by the Pediatric Brain Tumor Consortium was looking at that drug in a variety of children with low-grade glioma that had recurred. But the data that I specifically presented a couple weeks ago at ISPNO was looking at a unique arm of that study called 29C, and it was asking a very specific question.

So one of the unanswered questions in targeted therapies in low-grade glioma is whether retreatment with the same drug is an effective strategy. So for example, if a child responds or is stable on a targeted therapy for several years, and then they stop the drug, and then they recur maybe 2 months later or 1 year later, if you reuse that same drug again is it an effective strategy?

And so there’s been some clinical implications that that may be the case, but no one’s ever tested it prospectively. And so our specific study looked at the drug selumetinib, the MEK inhibitor, in children who had been previously treated on our phase I and phase II trial and who had progressed after stopping the drug. And so we did a retreatment study. And so it looked at whether the retreatment with selumetinib in these patients was again effective.

And so what the study looked at was either if the patients had response again or if they were stable for at least 12 months or 12 cycles of the therapy. And we had specific statistical guidelines that we had to meet in order to measure success. And there were 35 children enrolled and we met all parameters of success that were predetermined by statistical design. So over 80% of the patients had at least stable disease for 12 months or more, and then a small fraction of them actually had responses as well.

And so what the study concluded was that retreatment using selumetinib if you recur after stopping the drug — not during using the drug — is an effective strategy moving forward. And this was the first time we’ve ever shown that prospectively in a large number of patients, that retreatment is an effective strategy.

Of course, it raises many other questions, but the specific question about whether it’s effective in terms of allowing for prolonged stability and response is something that we answered in our study.

I think historically people would often change to a different drug if they recurred after stopping. There have been some people in the last several years who have tried off-study retreatment and have seen that it’s effective and so have been slowly incorporating that into their practice. But I think these data prospectively show more definitively that that is an appropriate strategy and should be strongly considered in this patient population.

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