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
Year: 2026
Type: article
Study design: Observational Study
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.
Source: Cancers
Authors: Michael Weichenthal, Dirk Debus, Lisa Zimmer, Imke von Wasielewski, Friedegund Meier, Thomas Tüting, Markus V. Heppt, Jessica C. Hassel, Fabian Ziller, Peter Mohr, Pia Dücker, Anca Sindrilaru, Edgar Dippel, Lucie Heinzerling, Marc Bender, Manar Aoun, Magdalena Walecki, Rudolf Herbst, Yenny Angela, Rudolf Stadler, Sebastian Haferkampf, Claus-Detlev Klemke, Kjell Matthias Kaune, Johannes Wohlrab, Ulrike Leiter, Nessr Abu Rached, Jochen Utikal, Gaston Schley, Jens Ulrich, Erwin Schultz, Christoffer Gebhardt, Patrick Terheyden, Ralf Gutzmer, Dirk Schadendorf
Institutions: University Hospital Schleswig-Holstein, Nuremberg Hospital, Paracelsus Medizinische Privatuniversität, Essen University Hospital, University Hospital Carl Gustav Carus, Nationales Centrum für Tumorerkrankungen Dresden, Technische Universität Dresden, University Hospital Magdeburg, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen, Heidelberg University, University Hospital Heidelberg, National Center for Tumor Diseases, German Red Cross, Elbe Kliniken Stade-Buxtehude, Klinikum Dortmund, University Hospital Ulm, Klinikum Ludwigshafen, LMU Klinikum, Ludwig-Maximilians-Universität München, Novartis (Switzerland), Helios Klinikum Erfurt, Johannes Wesling Klinikum Minden, Ruhr University Bochum, University Hospital Regensburg, University of Freiburg, Martin Luther University Halle-Wittenberg, Universitätsklinikum Tübingen, University of Tübingen, German Cancer Research Center, University Medical Centre Mannheim, Helios Hospital Schwerin, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, University of Lübeck
Language: English
Topic: Melanoma and MAPK Pathways
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
Funder: Novartis
OpenAlex ID: W7130390134