Comparing the impact of nivolumab & ipilimumab combination therapy vs. dabrafenib & trametinib on outcomes in malignant melanoma patients: A global propensity-matched retrospective cohort study.

Abstract

e21604 Background: Malignant melanoma is a highly aggressive skin cancer with a high mortality rate. Thenivolumab-ipilimumab combination therapy and dabrafenib-trametinibtherapy are established regimens for treating malignant Melanoma, each with unique efficacy and safety profiles. This study utilizes global propensity-matched data to compare their impact on cardiovascular and other outcomes in malignant melanoma patients. Methods: We utilized a real-world global database to identify all malignant melanoma patients from 2005 to 2025. Patients were stratified into two cohorts based on their treatment regimen: nivolumab and ipilimumab combination therapy (Cohort 1) or dabrafenib and trametinib (Cohort 2). Propensity score matching (PSM) was performed to balance basic demographics and common comorbidities between the cohorts. Outcomes were assessed using the platform analytical tools. Risk Ratios (RR) with 95% confidence interval (CIs) and p-values were calculated. Results: Our analysis included a total of 3,956 patients with malignant melanoma, with 1,978 patients in each cohort after PSM.Cohort 1 was associated with a lower risk of all-cause mortality compared to Cohort 2(RR: 0.82, 95% CI: 0.75-0.90, p < 0.001). No significant differences were observed for acute myocardial infarction (RR: 0.87, 95% CI: 0.61-1.25, p = 0.45), cardiac arrest (RR: 0.55, 95% CI: 0.26-1.14, p = 0.1), or acute ischemic stroke (RR: 0.83, 95% CI: 0.36-1.92, p = 0.7).Patients in Cohort 1 had a lower risk of new heart failure (RR: 0.80, 95% CI: 0.65-0.99, p = 0.04) but a trend towards higher risk of atrial fibrillation/flutter (RR: 1.14, 95% CI: 0.95-1.40, p = 0.16) compared to Cohort 2. The risk of acute hemorrhagic stroke was significantly lower in Cohort 1(RR: 0.61, 95% CI: 0.47-0.79, p < 0.001).Other outcomes, such as HLH (RR: 1.0, 95% CI: 0.41-2.40, p = 1.0), hypothyroidism (RR: 1.81, 95% CI: 1.60-2.04, p < 0.001), and acute kidney injury (RR: 1.06, 95% CI: 0.90-1.24, p = 0.51), varied between the groups. The readmission rate (RR: 1.33, 95% CI: 0.97-1.83, p = 0.08) did not differ significantly, but the incidence of secondary tumors was higher in Cohort 1 (RR: 1.18, 95% CI: 1.02-1.36, p = 0.03) Compared to Cohort 2. Conclusions: This study compares nivolumab-ipilimumab and dabrafenib-trametinib in melanoma patients. It shows that nivolumab-ipilimumab is associated with a lower risk of all-cause mortality and stroke but with a higher risk of hypothyroidism. It emphasizes the need for personalized treatment approaches that balance efficacy and risks.