Efficacy, safety and factors associated with disease progression in patients with unresectable (stage III) or distant metastatic (stage IV) BRAF V600-mutant melanoma: An open label, non-randomized, phase IIIb study of trametinib in combination with dabrafenib.

Autor: Saiag P; University of Paris-Saclay, UVSQ, EA4340, Boulogne-Billancourt 92100, France; APHP Hôpital Ambroise Paré, Department of Dermatology, F 92100, Boulogne-Billancourt, France. Electronic address: philippe.saiag@uvsq.fr., Robert C; Department of Dermatology, Institut Gustave Roussy, Villejuif, France., Grob JJ; Department of Dermatology, Aix-Marseille University, APHM, University Hospital Timone, Marseille, France., Mortier L; Université de Lille, INSERM U 1189, Service de Dermatologie, CHU Lille, Lille 59000, France., Dereure O; Department of Dermatology, CHU Montpellier, Montpellier, France., Lebbe C; Université de Paris, INSERM U976, Team 1, HIPI, Paris 75010, France; AP-HP Hopital Saint Louis, Service de Dermatologie, Paris 75010, France., Mansard S; Department of Dermatology, CHU Estaing, Clermont-Ferrand, France., Grange F; Department of Dermatology, CHU Reims, Reims, France., Neidhardt EM; Department of Medical Oncology, Centre Léon Bérard, Lyon, France., Lesimple T; Department of Medical Oncology, Eugene Marquis Center, Rennes, France., Machet L; Department of Dermatology, CHRU de Tours et Université François Rabelais de Tours, Tours, France., Bedane C; Department of Dermatology, CHU Limoges, Limoges, France., Maillard H; Department of Dermatology, CHRU de Tours et Université François Rabelais de Tours, Tours, France., Dalac-Rat S; Department of Dermatology, CHU Le Mans, Le Mans, France., Nardin C; Department of Dermatology, CHU Dijon, Dijon, France., Szenik A; Department of Dermatology, CHU de Besançon, Besançon, France., Denden A; Department of Medical Oncology, Novartis Pharma S.A.S.-France, Rueil-Malmaison, France., Dutriaux C; Department of Dermatology, CHU Bordeaux Hôpital St. André, Bordeaux, France.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2021 Sep; Vol. 154, pp. 57-65. Date of Electronic Publication: 2021 Jul 06.
DOI: 10.1016/j.ejca.2021.05.031
Abstrakt: Background: BRAF and MEK inhibitors combination, including dabrafenib (D) and trametinib (T) have transformed the treatment of BRAF V600-mutant advanced melanoma patients, including patients with brain metastasis (BM). In a large phase IIIb, single-arm, open-label, multicenter French study, we assessed safety, response to treatment, progression-free survival (PFS) and factors associated with progression, and stratified the population into risk groups.
Methods: Patients with unresectable, advanced, BRAF V600-mutant melanoma were included, including those with the presence of BM, Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2, elevated lactate dehydrogenase (LDH) or previous melanoma treatments. Responses were determined locally, without central review. PFS was estimated using the Kaplan-Meier analysis and modelled with multivariate Cox model. Risk subgroups were identified using a regression tree analysis.
Results: Between March 2015 and November 2016, 856 patients received at least one D + T dose. Overall, 92% had stage IV melanoma, 38% ECOG PS ≥1, 32% BM and 37.5% elevated LDH. Median PFS was 8.02 months (95% confidence interval [CI] 7.33-8.77). Significant factors associated with lower PFS were ECOG PS ≥1, elevated LDH, ≥3 metastatic sites and presence of BM. Patients with <3 metastatic sites, ECOG = 0 and no BM had the highest probability of PFS at 6 months (83%, 95% CI 76-87) and 12 months (56%, 95% CI 47-64), respectively.
Conclusions: This is the largest prospective study in advanced BRAF V600-mutant melanoma patients treated with D + T, conducted in conditions close to 'real-world practice'. We confirm previous findings that LDH, ECOG PS and ≥3 metastatic sites are associated with shorter PFS, but the real-world setting introduces BM as a major prognostic factor.
(Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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