Dr Hansford on HRQOL Outcomes With Tovorafenib in Pediatric BRAF-Altered Low-Grade Glioma

Our total scores are improved in multiple domains, including anxiety, cognition, and other features. Not only are we seeing great efficacy, which was presented previously, but diving into the QOL on this study is also showing the patients are feeling improved QOL with this new agent, as well."

Jordan R. Hansford, MD, lead, pediatric neuro-oncology, the Women’s and Children’s Hospital; lead, Pediatric Neuro-Oncology Group, the South Australia Health and Medical Research Institute; the South Australia ImmunoGenomics Cancer Institute, the University of Adelaide, discusses health-related quality-of-life (HRQOL) outcomes with the type II RAF inhibitor tovorafenib (Ojemda) in pediatric patients with 

-altered relapsed/refractory low-grade glioma from the phase 2 FIREFLY-1 trial (NCT04775485).

An exploratory analysis of the trial assessed HRQOL in patients with recurrent/refractory 

-altered pediatric low-grade glioma treated with tovorafenib. HRQOL was evaluated using the PedsQL 3.0 Cancer Module through parent and/or self reports for patients in arm 1 of the study.

2024 Society for Neuro-Oncology Annual Meeting

 showed that HRQOL generally remained stable or improved for most patients during the first year of treatment, Hansford reports. Improvements were noted across multiple domains, including anxiety and cognition, he adds. These findings complement previously reported efficacy data, emphasizing that tovorafenib not only provides clinical benefit but also enhances patients’ QOL, Hansford says.

Despite these encouraging results, long-term HRQOL analysis was limited by reduced completion of reports from parents and patients as the study progressed, Hansford notes. Although the phase 2 nature of the trial offers valuable insights into the short-term benefits of tovorafenib, the long-term impact of this therapy on HRQOL remains an important unanswered question. Given the potential for extended survival in pediatric patients, understanding how treatment affects their QOL over several years or after discontinuation is critical, Hansford emphasizes. Future studies will need to explore these aspects to assess the sustained impact of tovorafenib on overall wellbeing, he concludes.

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Jordan R. Hansford, MD, discusses health-related quality-of-life outcomes with tovorafenib in pediatric patients with BRAF-altered low-grade glioma.

Jordan Hansford, MD, clinical lead, Neuro-Oncology Group, Royal Children’s Hospital Melbourne, discusses the phase 2 FIREFLY-1 trial (NCT04775485), which is investigating the pan-RAF inhibitor tovorafenib (DAY101) in children and young adults patients with low-grade glioma.

 and the 2023 SNO Pediatric Neuro-Oncology Research Conference, FIREFLY-1 investigators presented efficacy and safety findings from this 3-arm phase 2 trial, Hansford says. FIREFLY-1 enrolled patients aged 6 months to 25 years with 

-altered tumors who experienced radiographic progression on at least 1 prior line of systemic therapy. Arm 1 of this trial (n = 77) enrolled patients with low-grade glioma harboring a known activating 

 V600E mutation. Arm 2 (n = 59) included patients with low-grade glioma harboring a known activating 

 alteration. Arm 3 is enrolling patients with locally advanced or metastatic solid tumors harboring a known activating 

 fusion whose disease relapsed after, progressed on, or was unresponsive to available therapies.

Patients in arm 1, including those with prior exposure to BRAF or MEK inhibitors, experienced marked responses to tovorafenib, Hansford emphasizes. In this arm, the overall response rate (ORR) per the Response Assessment in Neuro-Oncology – High-Grade Glioma (RANO-HGG) criteria was 67%, including a 6% complete response rate and a 61% partial response (PR) rate. Per RANO-HGG criteria, the clinical benefit rate (CBR) was 93%, and the CBR in patients who maintained a response or stable disease for at least 12 months was 71%. In addition, the ORR per the Response Assessment in Neuro-Oncology – Low-Grade Glioma criteria was 49%, including a PR rate of 26%.

The ORR per the Response Assessment in Pediatric Neuro-Oncology – Low-Grade Glioma criteria was 51%, including a PR rate of 25%.

In the safety population, which included patients from arms 1 and 2, the most common grade 3 or higher treatment-emergent adverse effects were maculopapular rash, fatigue, decreased appetite, and vomiting.

These data support the ongoing phase 3 FIREFLY-2 study (NCT05566795) of tovorafenib monotherapy vs standard of care chemotherapy in pediatric patients with 

-altered low-grade glioma, Hansford concludes.

Jordan Hansford, MD, discusses the phase 2 FIREFLY-1 trial, which is investigating the pan-RAF inhibitor tovorafenib (DAY101) in children and young adults with low-grade glioma.

Jordan Hansford, MD

Articles

Dr Hansford on HRQOL Outcomes With Tovorafenib in Pediatric BRAF-Altered Low-Grade Glioma

Dr Hansford on the FIREFLY-1 Trial of Tovorafenib in Pediatric Low-Grade Glioma