Can nivolumab and ipilimumab be used to treat melanoma brain metastases?

This study looked at the effectiveness and safety of nivolumab (Opdivo) alone compared to nivolumab in combination with ipilimumab (Yervoy) in patients with melanoma that had spread to the brain (metastasis). The study found that patients treated with a combination of ipilimumab and nivolumab responded to treatment better compared to treatment with nivolumab alone.

Immunotherapy is a type of therapy that boosts the immune system to help the body fight cancer. Immunotherapy such as ipilimumab and nivolumab have been shown to significantly improve the overall survival of patients with advanced melanoma compared with standard therapy.

In 25% of patients with advanced melanoma the cancer has spread to the brain and this can result in reduced survival.

Intracranial (within the skull) response refers to how effective a cancer treatment is at reducing tumour in the brain. This study was conducted because it is not known how effective nivolumab monotherapy or combination nivolumab plus ipilimumab is in active brain metastases.

This study was conducted at four cancer centres in Australia. Patients were split into three groups. Patients in group A and B had asymptomatic (no symptoms) brain metastases with no previous therapy aimed at the brain (local therapy). Patients in group C had brain metastases and local therapy had failed, or they had symptoms affecting their nervous system.

Patients in group A (35 patients) received nivolumab combined with ipilimumab every 3 weeks for four doses, then nivolumab every 2 weeks; patients in group B (25 patients) or group C (16 patients) received  nivolumab every 2 weeks. The study investigated the number of patients in each group who experienced an intracranial response at or 12 weeks after treatment started.

46% of patients in group A (nivolumab combined with ipilimumab) and 20% of patients in group B (nivolumab) achieved a decrease in brain tumour (intracranial response).  6% of patients in group C achieved an intracranial response.

At the end of the study, 16 (46%) of patients in group A, and 20 (80%) of  patients in cohort B displayed signs the cancer was progressing (growing more).  

Serious effects due to treatments occurred in 19 (54%) patients in group A, four (16%) in group B, and two (13%) in group C. The most common serious side effects were diarrhoea, inflammation of the colon and inflammation of the liver.

No deaths occurred because of study treatment. Nine (26%) patients in group A, one (4%) in cohort B, and one (6%) in cohort C stopped study treatment because of side affects.

The study concluded that asymtomatic patients with untreated brain metastases from melanoma may benefit from a combination of nivolumab combined with ipilimumab.

This study was funded by the pharmaceutical company which manufactures nivolumab and ipilimumab. Both patients and researchers knew who was getting which study drug (open-label), this can impact results. There was a small number of patients in each group which can make it difficult to draw conclusions from the results.

Speak to your medical oncologist about combination immunotherapy for brain metastases.