Immunotherapy and targeted therapy for advanced melanoma: a review

The authors reviewed immunotherapies and targeted therapies for the treatment of advanced melanoma. 

In advanced melanoma (stage IV), cancer spreads from the skin to other parts of the body. Immunotherapy and targeted therapy are promising treatment options for this disease. These therapies have shown improvement in overall survival (patients who are still alive after treatment) in patients over a 5-year period.

Immunotherapy uses the body’s own immune system to fight cancer. Ipilimumab (Yervoy) is a common immunotherapy for this disease. Targeted therapy attacks specific genes such as BRAF. These genes are often mutated (permanently changed) in melanoma patients. BRAF inhibitor is a targeted therapy, which stops certain cell signaling proteins in melanoma cells containing mutated BRAF genes.

A better understanding of these treatment options is needed to increase long-term patient survival.

The authors aimed to review the benefits and challenges of immunotherapy and targeted therapy for the treatment of advanced melanoma.

Immunotherapy

1,861 patients treated with ipilimumab were analyzed. The 3-year overall survival was 22%. During the 10-year follow-up, some patients were no longer receiving treatment, which indicated that treatment-free survival was possible with ipilimumab. Patients who received previous ipilimumab treatment followed by 3 mg/kg of ipilimumab had a 5-year overall survival of 16.5% to 17% compared to 17.6% to more than 49% in patients treated with 10 mg/kg. Patients treated with ipilimumab and dacarbazine (DTIC) had a 5-year survival of 18.2%. This was compared to 8.8% in patients who received dacarbazine only.

Nivolumab (Opdivo) and pembrolizumab (Keytruda) are other immunotherapies that have shown promising results. In a phase I study, 94 patients were treated with nivolumab. 28% showed an objective response (partial or complete disappearance of tumors) from 1.9 months to 24.9 months. In another phase I study, 117 patients were treated with pembrolizumab. 38% showed an objective response.

Targeted therapy

1-year overall survival was evaluated in a phase III study of vemurafenib (Zelboraf – a BRAF inhibitor). Overall survival was 55% for patients treated with vemurafenib. This was compared to 43% for patients treated with dacarbazine.

Dabrafenib (Tafinlar) and trametinib (Mekinist) are two approved targeted therapies. In a phase III trial of dabrafenib, progression–free survival (time following treatment before the disease progressed) was 5.1 months. This was compared to 2.7 months for patients treated with dacarbazine. In a phase III trial of trametinib, the progression free survival was 4.8 months. This was compared to 1.5 months for patients treated with chemotherapy.

The effectiveness of dabrafenib/ trametinib combination therapy was studied in a phase I/II trial. The objective response was 76% for the combination group and 54% for the dabrafenib only group.

Other strategies

Numerous combination therapies are being explored involving ipilimumab and a range of chemotherapies (DTIC, temozolomide [Temodar, TMZ]), immunotherapies (nivolumab) targeted therapies (BRAF inhibitors) and radiation therapies (directing a beam of radiation at the tumor site to kill cancer cells).

The authors concluded that immunotherapy and targeted therapy could increase overall survival for advanced melanoma patients. They further suggested that combination therapy could increase patient benefit.