Nivolumab with ipilimumab compared to ipilimumab only in advanced melanoma

The authors compared nivolumab (Opdivo) in combination with ipilimumab (Yervoy) to ipilimumab alone in the treatment of advanced melanoma.

In the advanced stages of melanoma (stage III/IV), cancer spreads from the skin to other parts of the body. In many melanoma patients, BRAF genes are mutated (permanently changed).  These genes are important in cell signaling. BRAF inhibitors are one of the standard treatments used to treat BRAF mutated melanoma. These drugs stop certain cell signaling proteins used by melanoma cells containing the mutated BRAF gene. Although these drugs improve overall survival (patients who are still alive after treatment), the average duration of response to the treatment is less than 1 year. Duration of response is from the time the response (decrease in tumor size) is achieved until regrowth of the tumor is detected. Therefore, there is a need for alternate treatments, particularly for patients who do not have BRAF mutations.

Immunotherapy is an alternate and more general treatment. It uses the body’s own immune system to attack the tumor cells and kill them. Nivolumab and ipilimumab are examples of this therapy that works by inhibiting important proteins in the immune system. Several studies have indicated that combining these drugs could improve objective response (partial or complete disappearance of tumor), duration of response and overall survival.

Further studies are needed to establish the utility of combining nivolumab with ipilimumab in the advanced stages of this disease.

The authors aimed to compare nivolumab in combination with ipilimumab to ipilimumab only in the treatment of advanced melanoma.

142 advanced melanoma patients were included in this study. Patients were separated into 2 groups. In group 1, 109 patients had tumors with non-mutated BRAF genes. In group 2, 33 patients had tumors with mutated BRAF genes. None of the patients had previously received any treatment. All patients were randomly assigned to receive ipilimumab combined with nivolumab or ipilimumab combined with a placebo (inactive drug used instead of the active drug).

In group 1, 61% of patients who received the combination treatment achieved objective response rates. This was compared to 11% in patients treated with ipilimumab only. 22% of patients in group 1 experienced a complete disappearance of tumors (complete response) when treated with the combination treatment compared to 0% treated with ipilimumab only. The average progression-free survival (time following the treatment before disease progressed) was 4.4 months in group 1 patients treated with ipilimumab alone. Complete response rate and progression-free survival were similar in group 2 patients.

Severe (grade 3) or life-threatening (grade 4) treatment-related side effects were experienced by 54% of patients receiving the combination treatment. 24% of patients receiving ipilimumab only experienced grade 3 or grade 4 side effects. Colitis (swelling of the colon) and diarrhea were among the most common side effects experienced by both treatment groups. 

The authors concluded that ipilimumab together with nivolumab was well tolerated. They further found that the combination treatment was more effective in eliminating tumors compared to ipilimumab alone.