Is dabrafenib with trametinib treatment effective before surgery for patients with unresectable advanced-stage melanoma?

This study investigated the effectiveness of dabrafenib (Tafinlar) plus trametinib (Mekinist) treatment before surgery for patients with unresectable advanced-stage melanoma. The data showed that this treatment was effective before surgery and allowed for the removal of tumors.

Melanoma is an aggressive type of skin cancer. It has a high tendency to spread to other parts of the body (metastasis). In stage 3 or 4 melanoma, cancer has spread to nearby lymph nodes. The main form of treatment is the surgical removal of tumors. Tumors that cannot be removed surgically (unresectable) can be difficult to treat. Patients with unresectable tumors often have a poorer prognosis.

BRAF and MEK are the most common mutated (abnormal) genes in melanoma. These mutations allow tumors to grow at a rapid rate. Using drugs that target these mutations can improve survival. Dabrafenib is a drug that targets BRAF-mutant cancer cells. Trametinib is a drug that inhibits MEK. It has been shown that dabrafenib combined with trametinib before surgery (neoadjuvant) was safe and effective for patients with resectable stage 3 melanoma. However, there are very few studies investigating the effectiveness of dabrafenib plus trametinib treatment before surgery for patients with unresectable advanced-stage melanoma.

This study involved 21 patients with unresectable metastatic stage IIIC/IV melanoma. All patients were treated with dabrafenib and trametinib for 8 weeks. All patients underwent then a PET/CT scan to scan for sufficient reduction of the tumor. If this was achieved, the patients were treated by surgical removal of the tumor (resection). The average follow-up time was 50 months.

85.7% (18) of the patients achieved sufficient reduction of the tumor and underwent surgery. 17 of these patients had complete removal of the tumor. The average survival without cancer coming back was 9.9 months in patients undergoing surgery. The average survival without cancer worsening was 12.4 months. The overall survival rate at 1-year was 100% and at 2-years was 85%.

The most common side effects after dabrafenib/trametinib treatment were fever, chills, fatigue, nausea, and muscle pain.

This study concluded that treatment with dabrafenib and trametinib before surgery for patients with unresectable advanced stage melanoma was effective to allow for resection of the tumor.

The sample size was very small. During this study, dabrafenib and trametinib treatment after surgery became the new standard of care in patients with resectable stage III melanoma.