Is a combination of ipilimumab and nivolumab a safe and effective standard treatment for advanced melanoma?

This review investigated whether ipilimumab (Yervoy) and nivolumab (Opdivo) combined treatment would be a safe standard treatment for advanced melanoma. Researchers concluded that this combined treatment cannot be considered the standard treatment yet due to the lack of overall survival studies and high rates of toxicity. 

In the past 5 years, the 1-year overall survival rate of advanced melanoma patients has improved from 25-30% to over 70%. These improvements are due to new drug therapies, such as BRAF inhibitors (for patients with a mutation, or permanent change, in the BRAF gene) and treatments that stimulate the immune system to attack tumor cells (such as ipilimumab and nivolumab). Prior studies concluded an added effectiveness in ipilimumab/ nivolumab combined treatment in patients without a BRAF mutation.

The current review examined the research to date on the safety and effectiveness of the combined ipilimumab/nivolumab treatment.

In a study including 915 metastatic melanoma patients, the response rate for the combined treatment was 58%, compared to 44% for nivolumab alone and 19% for ipilimumab alone. Time to progression was an average of 11.5 months with the combination treatment, compared to 6.9 months for nivolumab alone and 2.9 months for ipilimumab alone. 46% of those receiving the combination treatment saw 18 months without disease progression, compared to 39% for nivolumab alone and 14% for ipilimumab alone. Overall survival (time from treatment until death from any cause) rate has not yet been defined.

The combined treatment was associated with an increase of overall negative side effects (96% of patients) compared with nivolumab alone (82%) and ipilimumab alone (86%). 55% of patients had severe side effects in the combined treatment, compared with 16% for nivolumab alone and 27% for ipilimumab alone. The most common were diarrhea (9.3%), alterations in liver function (6.1% to 8.3%) and colon inflammation (7.7%). Most side effects were manageable and resolved with standard treatment.

This review suggested that while ipilimumab and nivolumab combined treatment improved response and time to progression, it cannot be considered the standard treatment yet due to a lack in overall survival information and increased toxicity.