Does targeted therapy improve the outcome of patients treated with stereotactic radiosurgery for brain metastasis in melanoma?

The aim of this study was to evaluate the outcomes of combining stereotactic radiosurgery (SRS) with BRAF inhibitors for brain metastasis in patients with melanoma. The study found that adding BRAF inhibitors to STS improved patient outcomes.

Melanoma is one of the most aggressive forms of skin cancer. Treatment for melanoma includes surgery to remove the tumor. In more advanced melanoma, the tumor can spread to other parts of the body (metastasis). Patients with metastatic melanoma have limited treatment options. Brain metastasis are particularly hard to treat.

Stereotactic radiosurgery (SRS) is commonly used to remove the BM. SRS can directly target the tumor in the brain, rather than targeting the whole brain. SRS uses high-energy radiation to kill cancer cells by damaging their DNA.

Following surgery, patients can be given targeted therapy (TT) to ensure all the tumor cells are killed. Tumor cells develop specific genetic changes to help them survive and grow. One of these changes is in the BRAF gene. TT such as BRAF inhibitors stops these genetic changes from working. BRAF inhibitors such as vemurafenib (Zelboraf), dabrafenib (Tafinlar), and encorafenib (Braftovi) have improved the outcomes of patients with advanced melanoma. However, it is unclear how beneficial BRAF inhibitors can be following SRS in patients with BM.

This study evaluated data from 976 patients in 8 trials. All patients had BM from melanoma. 728 patients were treated with SRS alone. 244 patients were treated with SRS and BRAF inhibitors (combination group).

Patients treated with combination therapy had a 33% higher chance of a better survival following surgery. Data from 3 studies showed that patients who received BRAF inhibitors during or after SRS therapy had a 61% higher chance of a better survival.

6 trials reported on how well therapy controlled the tumor within the brain. Patients treated with SRS + BRAF inhibitors were 46% less likely to have progression of the disease in the brain.

Side effects associated with BRAF inhibitors such as vemurafenib and dabrafenib were increased liver function tests, joint pain, skin cancer, seizures, and skin thickening. 3 trials reported bleeding in the brain as a side effect of combination therapy. Patients who were given combination therapy were 3.16 times more likely to have a brain bleed compared to those who received SRS alone.

 The study concluded that patients with BM from melanoma treated with SRS and BRAF inhibitors had a better outcome than SRS alone.

In some studies, patients had received other therapy before the study. Not all studies reported the same outcomes.