Combination treatment with nivolumab and ipilimumab in untreated advanced melanoma

The authors evaluated the effect of nivolumab (Opdivo) or ipilimumab (Yervoy) alone, or in combination in advanced melanoma. The authors found out that the combination therapy was more effective than treatment with either of the single drugs. 

In advanced melanoma (stages 3 and 4), cancer spreads from the skin to other parts of the body. Immunotherapy is a promising treatment option for this disease. Immunotherapies stimulate the immune system to fight cancer. Nivolumab and ipilimumab are examples of immunotherapies that work by inhibiting (blocking) PD-1, an important protein in the immune system. Inhibiting PD-1 triggers the immune system to attack tumor cells and kill them.

A previous phase 2 clinical trial examining treatment with a combination of these two drugs had shown an improved response rate (complete or partial disappearance of tumors) in advanced melanoma patients. Further studies are needed to confirm these results. 

The authors aimed to compare the effect of combination therapy of nivolumab with ipilimumab to that of single therapy with either drug in advanced melanoma patients.

945 patients were included in this study. All patients were previously untreated and had tumors that could not be removed by surgery.  Patients were randomly divided into 3 groups. 314 patients in group 1 received nivolumab plus ipilimumab. 316 patients in group 2 received nivolumab only. 315 patients in group 3 received ipilimumab only. The follow-up time was 12.2 to 12.5 months. Progression-free survival (PFS, the time following treatment before the disease progressed) was evaluated.  

The average PFS was 11.5 months in group 1, 6.9 months in group 2, and 2.9 months in group 3. For patients who had tumors that included the PD-1 protein, the average PFS was 14 months in both group 1 and group 2. For those who did not include PD-1, the PFS was 11.2 months in group 1 and 5.3 months in group 2 patients.

Severe (grade 3) or life-threatening (grade 4) treatment-related adverse events were reported. These affected 55% of patients in group 1, 16.3% of patients in group 2, and 27.3% patients in group 3. Adverse events included diarrhea, fatigue, and itching of the skin.

The authors concluded that combination therapy of nivolumab and ipilimumab significantly improved progression-free survival in previously untreated melanoma patients.