Evaluating treatment options after surgery for patients with high-risk melanoma.

The aim of this study was to evaluate different types of therapy after surgery for patients with high-risk melanoma. The study found that add-on targeted therapy or immunotherapy was likely to decrease the risk of disease progression in these patients.

Melanoma is a form of skin cancer. Treatment for early-stage melanoma includes surgery to remove the tumor. For more advanced disease, some patients need add-on therapy following surgery to ensure all the cancer cells are killed. Add-on therapy options include immunotherapy (IT) and targeted therapy (TT). IT activates the patient’s immune system to locate and kill the cancer cells. Some tumors have specific genetic changes that help them to survive. TT targets these genetic changes to kill the cancer cells.

While there are lots of IT and TT options for use as add-on therapy, it is not clear which is the best option for patients with high-risk melanoma. It is also not known whether patients' age, stage of melanoma, or whether they have genetic changes impacts their response to therapy after surgery.

This study evaluated data from 5 randomized trials. Overall, 3505 patients with high-risk melanoma were evaluated. Patients were treated with a placebo or an IT/TT. IT included ipilimumab (Yervoy), pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab + nivolumab. TT included vemurafenib (Zelboraf) and the combination dabrafenib (Tafinlar) + trametinib (Mekinist).

Patients who were given any type of additional therapy after surgery were 43% more likely to have an improved survival without disease recurrence. Additional therapy with ipilimumab + nivolumab was associated with a 77% improved survival without recurrence in patients with stage IV melanoma. Patients treated with either pembrolizumab or nivolumab were 43-44% more likely to survive without disease recurrence.

Patients who had a BRAF mutation treated with dabrafenib + trametinib had a 51% lower risk of relapse.

Patient age or spread to the lymph nodes did not impact their response to add-on therapy. In patients with ulcerated melanoma (breakdown of the skin over the melanoma), ITs like pembrolizumab or ipilimumab were associated with higher effectiveness.

The highest risk of severe side effects was associated with nivolumab + ipilimumab (82%), followed by ipilimumab (54%), and vemurafenib (59%).

This study showed that add-on IT or TT after surgery was beneficial for patients with high-risk melanoma regardless of age or stage. 

The therapies were all compared to placebo. No trial compared one therapy to another directly. Patient characteristics varied between trials.