Longer Follow-Up Confirms Relapse-Free Survival Benefit With Adjuvant Dabrafenib Plus Trametinib in Patients With Resected <i>BRAF</i> V600-Mutant Stage III Melanoma.
View/ Open
Date
2018-12ICR Author
Author
Hauschild, A
Dummer, R
Schadendorf, D
Santinami, M
Atkinson, V
Mandalà, M
Chiarion-Sileni, V
Larkin, J
Nyakas, M
Dutriaux, C
Haydon, A
Robert, C
Mortier, L
Schachter, J
Lesimple, T
Plummer, R
Dasgupta, K
Haas, T
Shilkrut, M
Gasal, E
Kefford, R
Kirkwood, JM
Long, GV
Type
Journal Article
Metadata
Show full item recordAbstract
Purpose Dabrafenib plus trametinib improved relapse-free survival (RFS) versus placebo (hazard ratio [HR], 0.47; P < .001) in patients with resected BRAF V600-mutant stage III melanoma (BRF115532; COMBI-AD; ClinicalTrials.gov identifier: NCT01682083). We present an updated RFS analysis on the basis of extended study follow-up and a cure-rate model analysis to estimate the fraction of patients expected to remain relapse free long term.Methods In this phase III trial, patients with resected BRAF V600-mutant stage III melanoma were randomly assigned to 12 months of adjuvant dabrafenib plus trametinib versus placebo. We report updated RFS (primary end point) and distant metastasis-free survival. RFS was also analyzed by subgroups defined by baseline disease stage (American Joint Committee on Cancer 7th and 8th editions), nodal metastatic burden, and ulceration status. The fraction of patients who remained relapse free long term was estimated using a Weibull mixture cure-rate model.Results At median follow-up of 44 months (dabrafenib plus trametinib) and 42 months (placebo), 3- and 4-year RFS rates were 59% (95% CI, 55% to 64%) and 54% (95% CI, 49% to 59%) in the dabrafenib plus trametinib arm and 40% (95% CI, 35% to 45%) and 38% (95% CI, 34% to 44%) in the placebo arm, respectively (HR, 0.49; 95% CI, 0.40 to 0.59). Distant metastasis-free survival also favored dabrafenib plus trametinib (HR, 0.53; 95% CI, 0.42 to 0.67). The estimated cure rate was 54% (95% CI, 49% to 59%) in the dabrafenib plus trametinib arm compared with 37% (95% CI, 32% to 42%) in the placebo arm. Subgroup analysis of RFS demonstrated similar treatment benefit regardless of baseline factors, including disease stage, nodal metastatic burden, and ulceration.Conclusion Longer follow-up confirmed RFS benefit with dabrafenib plus trametinib. Subgroup analysis suggested that dabrafenib plus trametinib benefited patients regardless of baseline factors.
Collections
Subject
Humans
Melanoma
Skin Neoplasms
Oximes
Imidazoles
Pyridones
Pyrimidinones
Proto-Oncogene Proteins B-raf
Antineoplastic Combined Chemotherapy Protocols
Adjuvants, Immunologic
Disease-Free Survival
Treatment Outcome
Drug Administration Schedule
Follow-Up Studies
Double-Blind Method
Age Factors
Sex Factors
Dose-Response Relationship, Drug
Time Factors
Internationality
Adult
Middle Aged
Female
Male
Research team
Melanoma and Kidney Cancer
Language
eng
License start date
2018-12
Citation
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2018, 36 (35), pp. 3441 - 3449