Results of a Phase II/III study showed that patients who were given Tafinlar plus Mekinist saw an overall response rate of 47% vs. 11% for those who received standard chemotherapy only.
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Swiss pharmaceutical company Novartis announced the results of a Phase II/III study showing that the combination of the targeted therapies Tafinlar (dabrafenib) and Mekinist (trametinib) outperforms chemotherapy in pediatric low-grade glioma (pLGG) patients harboring the BRAF V600 mutation.
If approved, the drug combo could supplant chemotherapy as the standard of care for children suffering from this brain cancer.
Revealed during an oral presentation at the 2022 Annual Meeting of the American Society of Clinical Oncology (ASCO), the findings showed that patients who were given Tafinlar plus Mekinist saw an overall response rate (ORR) of 47%. On the other hand, those who received standard chemotherapy only experienced an ORR of 11%.
Novartis’ drug pair also led to significantly better survival outcomes. Over a median follow-up period of 18.9 months, children who received Tafinlar plus Mekinist had a median progression-free survival (PFS) of 20.1 months, nearly three times as long as the 7.4-month PFS in the chemotherapy arm.
“These results show dabrafenib and trametinib demonstrate an improvement over chemotherapy for children and adolescents with BRAF V600 low-grade gliomas,” Eric Bouffet, M.D., FRCPC, senior associate Scientist Emeritus at The Hospital for Sick Children in Toronto said in a statement.
The Phase II/III study enrolled 110 pLGG patients aged 1 to 17 years who were randomly assigned to receive standard-of-care intravenous chemotherapy or the Tafinlar-Mekinist combination treatment. For the first time, a new liquid formulation of the drug pair was used, making it easier to administer.
Aside from better survival and treatment response, the drug combo likewise led to a better patient experience. After a year of follow-up, tumors shrank in 89% of children in the Tafinlar-Mekinist arm, as opposed to only 70% of their comparators receiving chemotherapy. With fewer grade 3 or higher adverse events, Tafinlar plus Mekinist also bested chemotherapy in terms of safety. These factors may have contributed to the better quality of life reported by patients who received the combination treatment.
“These young patients and their families experience a heavy burden of care as BRAF V600 low-grade glioma poses a risk of neurological impairment and current standard-of-care treatment is intravenous and associated with frequent trips to the cancer clinic or hospital,” Jeff Legos, executive vice president, global head of oncology and hematology development at Novartis, said. “Tafinlar plus Mekinist has shown unprecedented efficacy, and we will work with health authorities to bring these children the possibility of a more effective and easier to administer liquid oral treatment option as quickly as possible.”
Glioma is the most common type of brain cancer in children, and the BRAF V600 genetic mutation is present in up to 20% of LGG cases. Aberrations in the BRAF gene are known to make solid tumors more aggressive, and children carrying such mutations have been shown to suffer worse clinical outcomes.
While Tafinlar plus Mekinist is routinely used to treat other malignancies, such as metastatic non-small cell lung cancer with a certain type of abnormal BRAF V600E gene and to prevent melanomas with a BRAF gene from returning after surgery, its use is currently not approved for brain cancer in children.
Along with a general lack of treatment options, these patients are left to endure the heavy burden of side effects and poor outcomes associated with standard chemotherapy. According to Novartis, data from this Phase II/III study will form part of regulatory applications to make its drug combo available to this patient population.
