# COMBI-EU: Real-World Evidence on Adverse Event Management and Time on Therapy with Adjuvant Dabrafenib Plus Trametinib in Patients with BRAF V600-Mutant Melanoma

## TL;DR

The COMBI-EU study found that better management of treatment side effects improved adherence to melanoma therapy, especially for managing fever.

## Contribution

This study provides real-world evidence on how adverse event management impacts treatment adherence in BRAF V600-mutant melanoma patients.

## Key findings

- High-level adverse event management showed a trend toward improved treatment adherence.
- Pyrexia management was statistically significant in improving treatment adherence.
- App-based health tracking did not influence treatment adherence.

## Abstract

The prospective, non-interventional COMBI-EU study investigated the impact of adverse event management, and app-based health-tracking on the treatment adherence of patients with stage III BRAF V600 mutant cutaneous melanoma. Between July 2019 and December 2023, 225 patients who received adjuvant dabrafenib and trametinib in a real-world clinical practice were included at 31 treatment centers in Germany. High-level treatment-related adverse event management showed a trend toward improved treatment adherence (HR: 0.74; [0.49–1.14]), which was statistically significant for pyrexia. Optional use of a health-tracking app did not affect treatment adherence.:

Background/Objectives: Malignant melanoma is a highly aggressive cancer associated with significant mortality, underscoring the need for continued research efforts. COMBI-EU (NCT03944356) is a prospective, non-interventional study that aims to assess adjuvant dabrafenib and trametinib usage in clinical practice, the impact of AE management, and the usage of app-based documentation on treatment adherence. Methods: Adults with complete surgical resection of stage III BRAF V600-mutant cutaneous melanoma were included. The primary endpoint was median time on treatment (TOT). Adverse event (AE) management was classified as either a high or low level of management. The rating of AE management based on a self-developed algorithm and rules from COMBI-APlus was used to analyze the impact of AE management on TOT. App-based documentation of medication intake and patient-reported outcomes (CANKADO PRO-React; version 6.0, 06.03.2019) was offered. Results: For 225 patients, the median TOT was 11.8 months (95% confidence interval [CI]: 11.7, 12.0). Treatment was completed by 138 patients (61.3%); 37 (16.4%) discontinued due to treatment-related AEs (TRAEs). TRAEs (≥1) were experienced by 181 patients (80.4%); the most common was pyrexia (38.2%). High-level AE management showed a trend toward improved treatment adherence (high versus low level: hazard ratio [HR]: 0.74; 95% CI: 0.49, 1.14); this improvement was significant with pyrexia management (HR: 0.52; 95% CI: 0.29, 0.93). Seventy-nine (35%) and 33 patients (15%) intended to use and eventually used the app, respectively. A similar proportion of patients remained on treatment for 12 months irrespective of app usage (use, 39.4% vs. non-use, 36.5%). Conclusions: High-level TRAE management showed a trend toward improved treatment adherence, which was statistically significant for pyrexia. Optional use of an app did not influence treatment adherence.