A groundbreaking clinical trial is bringing renewed hope to children with an incurable form of paediatric brain cancer.

The FIREFLY-1 trial tested the efficacy of oral drug, tovorafenib, in patients with BRAF-altered (a genetic mutation), relapsed or progressive paediatric low-grade glioma (pLGG), with results showing a 50 per cent tumour shrinkage in two thirds of patients. 

Paediatric low-grade glioma is the most common childhood brain tumor and accounts for 30 to 50 per cent of all central nervous system tumours.  While slow growing, in many cases pLGG tumours are inoperable, and there are currently no approved systemic therapies for the vast majority of patients. 

Five-year-old Montana was diagnosed with pLGG at just a few months old. After surgery, chemotherapy and other medications were unsuccessful in managing her tumour, the trial has been game-changing. 

“She’s the healthiest and happiest that we’ve seen her,” Montana’s mum, Angie, said. 

“We have been really overwhelmed with how great the results have been and how much shrinkage there has been.” 

Montana’s oncologist, Associate Professor Geoff McCowage, a Senior Oncologist at The Children’s Hospital at Westmead (CHW), Advanced Cellular Therapeutics, Children's Cancer Research Unit, said the findings are significant and life-changing for patients like Montana, who have previously had no effective treatment options. 

“Having such a high response rate with minimal toxicity, compared to what we see with standard of care therapy, is very exciting,” A/Prof McCowage said. 

“In over 90 per cent of participants, the tumours have stopped growing, with two thirds of them having a dramatic shrinkage. That is an amazing outcome. It’s a really big breakthrough.

“It is hoped tovorafenib will become the first-choice treatment for pLGG, offering hope to families who previously would have been told nothing could be done.” 

The Children’s Hospital at Westmead and Sydney Children's are among 35 centres participating in the trial around the world.  

The trial was open to pLGG patients aged six months to 25 years who have undergone treatment, but their cancer had either worsened, was unresponsive or came back, with the drug is administered at home once each week. 

To date, Montana’s tumour has shrunk considerably, and she has experienced very few side effects, enabling her to live her best life possible as a five-year-old.  

Montana is soon to begin kindergarten and has big dreams of one day becoming a doctor, hoping to follow in the footsteps of those she now calls a second family.

The phase 2 FIRELY-1 results were recently published in the prestigious journal Nature Medicine. Next the drug is going to be tested in a direct comparison with older drugs to see if it can become a standard option in the future.