| Autor: |
Berking C; Department of Dermatology, Uniklinikum Erlangen, Comprehensive Cancer Center Erlangen-European Metropolitan Region Nürnberg, Friedrich-Alexander University (FAU), 91054 Erlangen, Germany., Livingstone E; Department of Dermatology, University Hospital Essen, and German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Debus D; Department of Dermatology, Nuremberg General Hospital-Paracelsus Medical University, 90419 Nuremberg, Germany., Loquai C; Department of Dermatology, Klinikum Bremen-Ost, Gesundheit Nord gGmbH, 28205 Bremen, Germany., Weichenthal M; Department of Dermatology, Skin Cancer Center, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany., Leiter U; Department of Dermatology, University Hospital Tuebingen, 72076 Tuebingen, Germany., Kiecker F; Department of Dermatology and Venereology, Vivantes Klinikum Berlin Neukölln, 12351 Berlin, Germany., Mohr P; Department of Dermatology, Elbe Kliniken Buxtehude, 21614 Buxtehude, Germany., Eigentler TK; Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany., Remy J; Novartis Pharma GmbH, 90429 Nuremberg, Germany., Schober K; Novartis Pharma GmbH, 90429 Nuremberg, Germany., Heppt MV; Department of Dermatology, Uniklinikum Erlangen, Comprehensive Cancer Center Erlangen-European Metropolitan Region Nürnberg, Friedrich-Alexander University (FAU), 91054 Erlangen, Germany., von Wasielewski I; Department of Dermatology, Skin Cancer Center Hannover, Hannover Medical School, 30625 Hannover, Germany., Schadendorf D; Department of Dermatology, University Hospital Essen, and German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany.; Comprehensive Cancer Center (Westdeutsches Tumorzentrum), University Hospital Essen, Essen & National Center for Tumor Diseases (NCT); NCT-West, Campus Essen & Research Alliance Ruhr, Research Center One Health, University Duisburg-Essen, 45147 Essen, Germany., Gutzmer R; Department of Dermatology, Johannes Wesling Medical Center, Ruhr University Bochum, 44801 Minden, Germany. |
| Abstrakt: |
Combined BRAF/MEK-inhibition constitutes a relevant treatment option for BRAF -mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in patients with advanced melanoma under routine clinical conditions. Progression-free survival (PFS) was the primary objective, and secondary objectives included overall survival (OS), disease control rate, duration of therapy, and the frequency and severity of adverse events. This study enrolled 472 patients at 55 German sites. The median PFS was 8.3 months (95%CI 7.1-9.3) and the median OS was 18.3 months (14.9-21.3), both tending to be longer in pre-treated patients. In the 147 patients with CNS metastases, PFS was similar in those requiring corticosteroids (probably representing symptomatic patients, 5.6 months (3.9-7.2)) compared with those not requiring corticosteroids (5.9 months (4.8-6.9)); however, OS was shorter in patients with brain metastases who received corticosteroids (7.8 (6.3-11.6)) compared to those who did not (11.9 months (9.6-19.5)). The integrated subjective assessment of tumor growth dynamics proved helpful to predict outcome: investigators' upfront categorization correlated well with time-to-event outcomes. Taken together, COMBI-r mirrored PFS outcomes from other prospective, observational studies and confirmed efficacy and safety findings from the pivotal phase III COMBI-d/-v and COMBI-mb trials. |
