dc.contributor.author | Hauschild, A | |
dc.contributor.author | Dummer, R | |
dc.contributor.author | Schadendorf, D | |
dc.contributor.author | Santinami, M | |
dc.contributor.author | Atkinson, V | |
dc.contributor.author | Mandalà, M | |
dc.contributor.author | Chiarion-Sileni, V | |
dc.contributor.author | Larkin, J | |
dc.contributor.author | Nyakas, M | |
dc.contributor.author | Dutriaux, C | |
dc.contributor.author | Haydon, A | |
dc.contributor.author | Robert, C | |
dc.contributor.author | Mortier, L | |
dc.contributor.author | Schachter, J | |
dc.contributor.author | Lesimple, T | |
dc.contributor.author | Plummer, R | |
dc.contributor.author | Dasgupta, K | |
dc.contributor.author | Haas, T | |
dc.contributor.author | Shilkrut, M | |
dc.contributor.author | Gasal, E | |
dc.contributor.author | Kefford, R | |
dc.contributor.author | Kirkwood, JM | |
dc.contributor.author | Long, GV | |
dc.date.accessioned | 2020-10-13T15:37:59Z | |
dc.date.issued | 2018-12 | |
dc.identifier.citation | Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2018, 36 (35), pp. 3441 - 3449 | |
dc.identifier.issn | 0732-183X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4144 | |
dc.identifier.eissn | 1527-7755 | |
dc.identifier.doi | 10.1200/jco.18.01219 | |
dc.description.abstract | 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. | |
dc.format | Print-Electronic | |
dc.format.extent | 3441 - 3449 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
dc.subject | Humans | |
dc.subject | Melanoma | |
dc.subject | Skin Neoplasms | |
dc.subject | Oximes | |
dc.subject | Imidazoles | |
dc.subject | Pyridones | |
dc.subject | Pyrimidinones | |
dc.subject | Proto-Oncogene Proteins B-raf | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Adjuvants, Immunologic | |
dc.subject | Disease-Free Survival | |
dc.subject | Treatment Outcome | |
dc.subject | Drug Administration Schedule | |
dc.subject | Follow-Up Studies | |
dc.subject | Double-Blind Method | |
dc.subject | Age Factors | |
dc.subject | Sex Factors | |
dc.subject | Dose-Response Relationship, Drug | |
dc.subject | Time Factors | |
dc.subject | Internationality | |
dc.subject | Adult | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.title | 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. | |
dc.type | Journal Article | |
rioxxterms.versionofrecord | 10.1200/jco.18.01219 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2018-12 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | |
pubs.issue | 35 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.) | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.) | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 36 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Melanoma and Kidney Cancer | en_US |
dc.contributor.icrauthor | Larkin, James | |