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

Weichenthal M, Debus D, Zimmer L, Wasielewski Iv, Meier F, Tüting T, Heppt M, Hassel JC, Ziller F, Mohr P, Dücker P, Sindrilaru A, Dippel E, Heinzerling L, Bender M, Aoun M, Walecki M, Herbst R, Angela Y, Stadler R, Haferkampf S, Klemke CD, Kaune KM, Wohlrab J, Leiter U, Rached NA, Utikal J, Schley G, Ulrich J, Schultz E, Gebhardt C, Terheyden P, Gutzmer R, Schadendorf D (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Cancers MDPI

Book Volume: 18

Article Number: 667

Journal Issue: 4

DOI: 10.3390/cancers18040667

Abstract

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.

Authors with CRIS profile

Markus Heppt Department of Dermatology Lucie Heinzerling Department of Dermatology

Involved external institutions

Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Paracelsus Medizinische Privatuniversität, Nürnberg DE Germany (DE) Universitätsklinikum Essen DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) DRK Krankenhaus Chemnitz-Rabenstein DE Germany (DE) Elbe Kliniken Stade-Buxtehude DE Germany (DE) Klinikum Dortmund DE Germany (DE) Martin-Luther-Universität Halle-Wittenberg (MLU) DE Germany (DE) Universitätsklinikum Tübingen DE Germany (DE) Ruhr-Universität Bochum (RUB) DE Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) HELIOS Kliniken DE Germany (DE) Harzklinikum Dorothea Christiane Erxleben DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Universität zu Lübeck DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Klinikum der Stadt Ludwigshafen am Rhein gGmbH DE Germany (DE) Novartis AG CH Switzerland (CH) EuMelaReg gGmbH (EMR) DE Germany (DE) Johannes Wesling Klinikum Minden DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE) Universitätsklinikum Freiburg DE Germany (DE) Klinikum Bremen-Ost DE Germany (DE)

How to cite

APA:

Weichenthal, M., Debus, D., Zimmer, L., Wasielewski, I.v., Meier, F., Tüting, T.,... Schadendorf, D. (2026). 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. Cancers, 18(4). https://doi.org/10.3390/cancers18040667

MLA:

Weichenthal, Michael, et al. "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." Cancers 18.4 (2026).

BibTeX: Download