COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma

Berking C, Livingstone E, Debus D, Loquai C, Weichenthal M, Leiter U, Kiecker F, Mohr P, Eigentler TK, Remy J, Schober K, Heppt M, von Wasielewski I, Schadendorf D, Gutzmer R (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Cancers MDPI

Book Volume: 15

Article Number: 4436

Journal Issue: 18

DOI: 10.3390/cancers15184436

Abstract

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.

Authors with CRIS profile

Carola Berking Lehrstuhl für Haut- und Geschlechtskrankheiten Markus Heppt Department of Dermatology

Involved external institutions

Universitätsklinikum Essen DE Germany (DE) Paracelsus Medizinische Privatuniversität, Nürnberg DE Germany (DE) Klinikum Bremen-Ost DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Universitätsklinikum Tübingen DE Germany (DE) Vivantes - Netzwerk für Gesundheit GmbH DE Germany (DE) Elbe Kliniken Stade-Buxtehude DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Novartis AG CH Switzerland (CH) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Johannes Wesling Klinikum Minden DE Germany (DE)

How to cite

APA:

Berking, C., Livingstone, E., Debus, D., Loquai, C., Weichenthal, M., Leiter, U.,... Gutzmer, R. (2023). COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma. Cancers, 15(18). https://doi.org/10.3390/cancers15184436

MLA:

Berking, Carola, et al. "COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma." Cancers 15.18 (2023).

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