Ipilimumab plus nivolumab is a standard first-line treatment for patients with intermediate and poor-risk advanced RCC. Serious or life-threatening side effects are relatively common with this combination. The aim of this phase 2 trial (PRISM) was to see if changing the treatment schedule for ipilimumab in combination with nivolumab can improve tolerability of this treatment without affecting patient survival.
During this study two nivolumab plus ipilimumab combination treatment schedules were compared. Patients with untreated advanced RCC were randomly put into two treatment groups in a ratio of 2:1: Group 1 was a modified schedule of ipilimumab combined with nivolumab every 12 weeks with nivolumab infusions every 2 weeks between combination doses. Group 2 was the standard treatment schedule of ipilimumab/nivolumab every 3 weeks for 4 doses followed by a standard dose of nivolumab every 2 weeks. Patients were treated until their disease progressed or they could not tolerate the side effects.
There were 192 patients in the study, more than two thirds of which (70%) had intermediate/poor-risk disease. Serious or life-threatening side effects were significantly lower in the patients on the modified ipilimumab schedule compared to the standard schedule (32.8% versus 53.1%, respectively). However, patients in the modified treatment group experience more diarrhoea, but less inflammation of the bowel (colitis), joint pain, liver problems, inflammation of the lungs (pneumonitis) and inflammation of the pituitary gland (hypophysitis). There were no differences in the survival outcomes for patients on the different treatment schedules.
This study showed that giving ipilimumab every 12 weeks instead of every 3 weeks, in combination with nivolumab, significantly reduced the number of serious or life-threatening side effects to treatment. The change in treatment schedule did not affect the survival outcomes of the patients.