Adjuvant therapy for the treatment of Melanoma.

The results of new studies to eliminate recurrences

Alessandra Bulotta
Article by Dr. Alessandra Bulotta
Oncologist specialized in Melanoma
San Raffaele Hospital in Milano

One of the absolute innovations in the treatment of cutaneous melanoma concerns adjuvant therapy.

Adjuvant therapy aims to reduce the risk of recurrences and improve the disease’s prognosis.

Today adjuvant therapy is suggested in cases of cutaneous melanoma with a high risk of relapse:
– Very thick or ulcerated primitive lesion (stage IIB-IIC)
or
– Metastatic positivity of lymph nodes (stage III)

In Italy the only adjuvant treatment available today is interferon (low or high dosage). There is not much agreement on the efficacy of the assay, but the emerging data from the collection of several studies globally document, and independently of dosage and duration, a benefit of interferon with 18% relative reduction on relapse-free survival and 11% on overall survival.

The importance of having drugs available for patients with at high risk of melanoma relapse is due to the fact that 70% and 80% of these patients will be affected again within 5 years from the diagnosis. The currently approved adjuvant therapies, interferon and, only in the United States, the anti-CTLA4 ipilimumab immunotherapeutic drug, are in fact rarely used because they have various limitations, including a non-negligible toxicity.

melanoma tumore della pelleRecently, data have been presented of studies conducted on patients operated for cutaneous melanoma in stages at high risk of relapse, using drugs that are still used and notoriously effective in patients with already metastatic melanoma ( check-point inhibitors such as ipilimumab and anti-PD1, as well as molecular target therapy with combined anti-BRAF and anti-MEK drugs).

In particular, they compared the adjuvant treatment of ipilimumab with nivolumab (CheckMate 238), or pembrolizumab (antibodies against the PD-1 / PDL-1 axis) with placebo (KEYNOTE 054) to define the role of anti-PD-1 antibodies in this setting. Both studies showed superiority over Ipilimumab. In particular in the CheckMate study, the recurrence-free survival rate with nivolumab at 18 months was 66.4%, compared to 52.7 with ipilimumab. Nivolumab reduced the risk of disease recurrence by 35% compared to ipilimumab. Nivolumab is therefore the first and only approved molecule (not yet, for the time being in Italy) for the adjuvant treatment of melanoma on the basis of a comparison study with an active treatment that has demonstrated a proven benefit of overall survival.

Other recently emerged data concern patients having the mutated BRAF gene. Adjuvant treatment with the combination of two targeted drugs, the BRAF dabrafenib inhibitor and the MEK trametinib inhibitor, reduced by 53% (more than halved), compared to placebo, the risk of relapse or death in patients with stage III melanoma and having the mutated BRAF gene. This is the main result of the international multi-center phase III study COMBI-AD.

We now have two different strategies in terms of mechanism of action, but I think they are equally valid in terms of efficacy and represent two very important choice options for patients with melanoma operated at high risk of relapse.

Current data will change, hopefully soon, clinical practice even in Italy.

Dr. Alessandra Buotta

Oncologist at the San Raffaele in Milano

Oncologist in the Division of Oncology at the San Raffaele Hospital in Milan. Dr. Bulotta performs clinical research activities focused on Malignant Melanoma, Lung cancer, Thyums cancer and Pleural mesothelioma.