The FDA approved a new regimen in 2018 for the treatment of BRAF V600 mutation-positive, inoperable, or metastatic undifferentiated thyroid cancer. This regimen consists of two targeted agents: dabrafenib (Tafinlar, GSK) + trametinib (Mekinist, GSK).
How does this new regimen work? What kind of patients is it suitable for? We invited Professor Lin Yansong and Professor Li Xiaoyi from Peking Union Medical College Hospital, the leading experts in thyroid cancer in China, to give you an analysis.
Which patients can be considered for the new regimen? Undifferentiated thyroid cancer with a BRAF mutation
Undifferentiated thyroid carcinoma (ATC) is rare, accounting for only about 1% of thyroid cancers, but is extremely malignant, with 90% of patients having extensive local invasion beyond the gland at the time of diagnosis and about 2/3 of patients having distant metastases at the time of diagnosis, or subsequently. The most common form of metastasis is metastasis.
These thyroid cancers progress very rapidly, leading to rapid airway obstruction and death, and even after surgery, they recur within 8 months in up to 92% of patients, with a median survival time of 4 to 5 months and less than 20% surviving for 1 year, making treatment very challenging.
Because of the difficulty of treatment, a combination of tools including surgery, radiotherapy, and drug therapy is important, with molecularly targeted drugs that target genetic alterations being the most promising therapy. mutations in the BRAF gene, the most common and important gene mutation in thyroid cancer, cause cancer cells to proliferate. This newly approved regimen inhibits the action of the BRAF V600 mutation and its subsequent pathways. Because of this, this regimen is only effective in patients with this mutation, and the FDA requires that genetic testing be done before the drug is administered, and that only the clear presence of the BRAF V600 mutation be treated with the new regimen.
What’s better about the new regimen?
Why did the FDA approve this combination? It was largely based on the results of a clinical study. In this study, the new regimen resulted in remission in 69% of patients, with a predicted 1-year overall survival rate of 80%. This is an exciting improvement.
Is the new regimen safe?
The two drugs in the combination regimen were marketed back in 2013, and this only expands their indication in undifferentiated thyroid cancer, with no additional, newer side effects in clinical use, with major side effects including fatigue, fever, and nausea, and a low incidence of serious adverse events (<5%).
Why do you want these two drugs in combination? Can’t you use one alone?
In the combination regimen, dabrafenib inhibits BRAF V600, the most common type of mutation in BRAF, and trametinib is a MEK inhibitor.MEK is in the downstream pathway of the BRAF gene, and they belong to the same signaling pathway ( MAPK signaling pathway). If only the mutated BRAF gene is inhibited, tumor cells may activate their downstream MEK and still continue to proliferate, and only if both mutated BRAF and MEK are inhibited can cancer cell growth be effectively stopped.
Can Chinese patients use this new regimen?
The two drugs are expected to be available in China as early as next year, and patients in China can expect to have access to this regimen by then.
If you want to learn more about the new drugs coming to market in 2018, click to read