OBJECTIVES : The objective of this study was to describe serious gastrointestinal (GI) events (including enterocolitis) among melanoma patients treated with ipilimumab, nivolumab, or combination ipilimumab/nivolumab.

METHODS : The Explorys Universe Database, electronic health records, was used for this analysis. Patients with ≥1 record for ipilimumab or nivolumab between March 1, 2011 and May 8, 2017 were selected and the index date was the first date of ipilimumab or nivolumab. Patients were required to be age ≥18 and to have ICD-9-CM or ICD-10-CM diagnosis for advanced melanoma in the 6-month baseline period. Patients were followed until the end of the study period or until first evidence of being no longer active in the database. Incident serious or severe GI events were measured during follow-up period. A Cox Proportional Hazard model estimated hazard ratio (HR) of any incident enterocolitis or ileus compared patients by index drug group (ipilimumab alone, nivolumab alone or combination), adjusting for age, sex, BMI, and comorbid conditions.

RESULTS : There were 904 melanoma patients who received a drug of interest, (607 ipilimumab monotherapy, 140 nivolumab monotherapy, and 157 patients with combination therapy). The average age at index was 63.5 years, and 65.2% male. The mean (SD) duration of treatment was longest for the combination therapy cohort (129.2 [126.5] days), followed by the nivolumab (120.8 [138.2] days) and ipilimumab cohorts (107.2 [174.7] days). The hazard of a GI event was significantly higher for combination ipilimumab/nivolumab patients (HR: 2.25; 95%CI 1.30, 3.90) than for ipilimumab patients. There was no increased risk for nivolumab versus ipilimumab patients (HR: 1.01; 95%CI 0.48, 2.11).

CONCLUSIONS : Among melanoma patients treated with ipilimumab and nivolumab, patients receiving combination therapy were 2.2 times more likely to have a serious or severe GI event compared to ipilimumab patients, suggesting additional clinical guidance needed for effective patient management of symptoms.