Are Targeted Combination Treatments More Beneficial in Advanced Melanoma?

A study published in the British medical journal found that combination treatments are more beneficial than single-agent treatment in advanced melanoma.

There have been major advances in the treatment of metastatic (advanced) melanoma in recent years. In particular, the discovery that mutations in the BRAF gene contribute to melanoma development has brought targeted treatment strategies to the forefront. The BRAF mutations targeted by these treatments activate a pathway called MAPK, which causes cells to grow and multiply uncontrollably. Blocking the products of this gene with certain agents can therefore prevent uncontrolled cell proliferation. Treatment uses agents that block BRAF, such as vemurafenib and dabrafenib, or agents that block the MAPK pathway, such as trametinib. However, reactivation of the MAPK pathway eventually leads to resistance to BRAF inhibitors, and the disease progresses again. Combining BRAF inhibitors with drugs that inhibit the MAPK pathway is thought to improve outcomes. A recent study therefore investigated whether combining dabrafenib and trametinib would be more effective than vemurafenib alone in metastatic melanoma.

The study followed approximately 700 previously untreated patients with BRAF-mutated metastatic melanoma. Some received vemurafenib alone, while others received dabrafenib and trametinib. The 12-month survival rate was 72% in patients receiving dabrafenib and trametinib, compared with 65% in those receiving vemurafenib alone. Time without disease progression was 11,4 months versus 7,3 months, respectively, and response rates were 64% versus 51%. Complete responses occurred in 47 patients in the dabrafenib and trametinib group, compared with only 27 in the vemurafenib group. These findings did not vary according to factors such as age, sex or mutation type.

In conclusion, earlier studies showed that dabrafenib plus trametinib was more beneficial than dabrafenib alone, and that vemurafenib plus cobimetinib was more beneficial than vemurafenib alone. By demonstrating that dabrafenib plus trametinib was superior to vemurafenib, this study also indicates that combination treatments are more beneficial than single-agent treatment in advanced melanoma. This strongly suggests that targeted combinations should play a much greater role in advanced melanoma treatment in the future. However, the findings need support from further studies.