Background: The use of anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) therapy (ipilimumab) and anti-programmed cell-death 1 (anti-PD1) agents (nivolumab and pembrolizumab) in advanced melanoma have been associated with immune-related adverse events (irAEs) including colitis. We aimed to estimate the incidence and the risk of colitis in elderly patients with advanced melanoma treated with anti-CTLA4 and anti-PD1 in the real-world setting.
Methods: Elderly patients (age ⩾ 65 years) diagnosed with advanced melanoma between 2011 and 2015 and treated with anti-CTLA4 or anti-PD1 agents were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. We estimated the risk of colitis from start of treatment up to 90 days from the last dose of therapy. We used the log-rank test and logistic regression with adjustment for potential confounders using the inverse probability of treatment weighting method. We conducted several sensitivity analyses.
Results: A total of 274 elderly patients with advanced melanoma were included in our cohort. The risk of colitis was similar between anti-PD1 users and anti-CTLA4 users based on log-rank test ( = 0.17) and logistic regression [odds ratio (OR) = 0.35, 95% confidence interval (95%CI) 0.04-2.79]. Sensitivity analyses for patients with all-stage melanoma showed a significantly lower risk of colitis in anti-PD1 compared with anti-CTLA4 treated patients based on log-rank test ( = 0.017) and logistic regression (OR = 0.21, 95%CI 0.09-0.53).
Conclusion: Elderly with advanced melanoma treated with anti-CTLA4 or anti-PD1 had a similar risk of developing colitis. However, there was a statistically significant difference in the risk of colitis between anti-CTLA4 or anti-PD1 users among all-stage-melanoma patients.
Plain Language Summary: While the anti-cancer agents known as immune-checkpoint inhibitors have had a great impact on the treatment of melanoma, they may also have side effects. This study estimated the risk of colitis, a chronic inflammation of the colon, in elderly patients with melanoma treated with anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) or anti-programmed cell-death 1 (anti-PD1) agents, using data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Overall, we found that the risk of colitis was not different between anti-PD1 users and anti-CTLA4 users with advanced-stage melanoma. However, after including patients across all stages of melanoma, we found a significantly lower risk of colitis with anti-PD1 compared with anti-CTLA4.