Effect of BRAF inhibitors in melanoma patients with disease progression

The authors analyzed the effectiveness of continued treatment with dabrafenib (Tafinlar) and vemurafenib (Zelboraf) in advanced melanoma after disease progression despite treatment with these drugs. 

In advanced melanoma (stage 3/4), cancer spreads from the skin to other parts of the body. BRAF genes are often mutated (permanently changed) in advanced melanoma. BRAF inhibitors (BRAFi) such as vemurafenib and dabrafenib stop (inhibit) certain cell signaling proteins in melanoma cells containing mutated BRAF genes. BRAF inhibitors have led to significant improvements in the treatment of melanoma. However, the return of cancer after treatment with BRAF inhibitors is common. Conflicting results have been reported regarding BRAFi treatment after disease progression.

To fully understand the effect of BRAFi on melanoma progression, a large patient-population based study is needed.

The authors aimed to examine the outcomes of melanoma patients who received BRAFi beyond disease progression.

114 BRAF-mutant stage 3 or 4 melanoma patients were included in this study. 69 patients received dabrafenib. 45 patients received vemurafenib.

68% achieved partial or complete disapperance of tumor. The average progression-free survival (time following treatment before the disease progresses) was 5.5 months. The average overall survival (time from treatment until death from any cause) was 10.9 months.

Overall 95 patients (83.3%) had disease progression following treatment. 37% of these patients did not receive any further treatment. 20% of patients switched to a different treatment. 39% of patients continued with BRAFi therapy for an average of 97 days.

56% of these 95 patients had melanoma spread outside the skull.18% of patients had melanoma spread both outside and inside the skull. 16% of patients had melanoma spread only inside the skull. The sites of metastases also varied in these 95 patients. 31% had cancer spread in a single site or organ. 48% had melanoma progress in existing metastases only. 18% of patients had cancer spread to new parts of body. 

The authors concluded that treatment with BRAFi might be continued in patients despite disease progression, if no other treatment option was available.