Are the side effects of trametinib combined with dabrafenib serious?

In melanoma and non-small cell lung cancer with the BRAF V600 mutation, an abnormal form of the BRAF protein is present that is involved in stimulating cell division, which contributes to the development of the cancer by allowing uncontrolled cell division. The combination of trametinib and dabrafenib may cause some side effects, and the most common side effects that may affect more than 1/5 of people are fever, fatigue, nausea, chills, headache, diarrhea, vomiting, joint pain, and rash.

The median duration of exposure to trametinib in patients treated with trametinib plus dabrafenib was approximately 11 months. In the COMBI-d and COMBI-v studies, greater than or equal to 20% of patients may experience fever, nausea, rash, chills, diarrhea, vomiting, hypertension, and peripheral edema. Discontinuation due to coadministration occurred in 11% of patients, including fever (1.4%) and decreased ejection fraction (1.4%). Coadministration resulted in dose reductions in 18% of patients, including fever (2.9%), neutropenia (1.9%), decreased ejection fraction (1.9%), and rash (1.9%), and 46% of patients resulted in dose interruptions due to coadministration, including fever (18%), chills (7%), vomiting (6%), and decreased ejection fraction (4.8%).

The original drug of trametinib has been launched in China and has entered the scope of Class B medical insurance, but it may only be purchased by patients who meet the indications of trametinib, such as BRAF V600 mutation-positive unresectable or metastatic melanoma. Its price is around 10,000 to 20,000 yuan. The reimbursement ratio is different in different regions, and the price is also different, making it expensive. The price of the Turkish version of the original drug Trametinib listed overseas is around RMB 7,900 (the price may fluctuate due to the exchange rate). Generic trametinib is also produced in other countries. The price of the Lao pharmaceutical factory is around RMB 2,950 (the price may fluctuate due to the exchange rate). The ingredients and efficacy of foreign generic drugs are basically the same as those of domestic and foreign original drugs.