dc.contributor.author | Valpione, S | |
dc.contributor.author | Carlino, MS | |
dc.contributor.author | Mangana, J | |
dc.contributor.author | Mooradian, MJ | |
dc.contributor.author | McArthur, G | |
dc.contributor.author | Schadendorf, D | |
dc.contributor.author | Hauschild, A | |
dc.contributor.author | Menzies, AM | |
dc.contributor.author | Arance, A | |
dc.contributor.author | Ascierto, PA | |
dc.contributor.author | Di Giacomo, A | |
dc.contributor.author | de Rosa, F | |
dc.contributor.author | Larkin, J | |
dc.contributor.author | Park, JJ | |
dc.contributor.author | Goldinger, SM | |
dc.contributor.author | Sullivan, RJ | |
dc.contributor.author | Xu, W | |
dc.contributor.author | Livingstone, E | |
dc.contributor.author | Weichenthal, M | |
dc.contributor.author | Rai, R | |
dc.contributor.author | Gaba, L | |
dc.contributor.author | Long, GV | |
dc.contributor.author | Lorigan, P | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-08-30T09:44:28Z | |
dc.date.available | 2022-08-30T09:44:28Z | |
dc.date.issued | 2018-03-01 | |
dc.identifier | S0959-8049(17)31486-7 | |
dc.identifier.citation | European Journal of Cancer, 2018, 91 pp. 116 - 124 | |
dc.identifier.issn | 0959-8049 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5342 | |
dc.identifier.eissn | 1879-0852 | |
dc.identifier.eissn | 1879-0852 | |
dc.identifier.doi | 10.1016/j.ejca.2017.12.007 | |
dc.description.abstract | BACKGROUND: Most metastatic melanoma patients treated with BRAF inhibitors (BRAFi) ± MEK inhibitors (MEKi) eventually progress on treatment. Along with acquired resistance due to genetic changes, epigenetic mechanisms that could be reversed after BRAFi discontinuation have been described. The purpose of this study was to analyse retrospectively outcomes for patients retreated with BRAF-directed therapy. PATIENTS AND METHODS: One hundred sixteen metastatic melanoma patients who received BRAFi-based therapy and, after a break, were rechallenged with BRAFi ± MEKi at 14 centres in Europe, US and Australia were studied, respectively. Response rate (RR), overall survival (OS) and progression-free survival (PFS) from the start of retreatment were calculated. RESULTS: The median duration of treatment was 9.4 months for first BRAFi ± MEKi treatment and 7.7 months for the subsequent treatment (immunotherapy 72%, other 17%, drug holiday 11%) after BRAFi discontinuation. Brain metastases were present in 51 (44%) patients at BRAFi retreatment. The RR to rechallenge with BRAFi ± MEKi was 43.3%: complete response (CR) 2.6%, partial response (PR) 40.7%, stable disease (SD) 24.8% and progressive disease 31.9%, 3 missing. Of 83 patients who previously discontinued BRAFi due to disease progression, 31 (37.3%) responded (30 PR and 1 CR) to retreatment. The median OS from retreatment was 9.8 months, and PFS was 5 months. Independent prognostic factors for survival at rechallenge included number of metastatic sites (hazard ratio [HR] = 1.32 for each additional organ with metastases, P < .001), lactic dehydrogenase (HR = 1.37 for each multiple of the upper normal limit, P < .001), while rechallenge with combination BRAFi + MEKi conferred a better OS versus BRAFi alone (HR = 0.5, P = .006). CONCLUSION: Rechallenge with BRAFi ± MEKi results in a clinically meaningful benefit and should be considered for selected patients. | |
dc.format | Print-Electronic | |
dc.format.extent | 116 - 124 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER SCI LTD | |
dc.relation.ispartof | European Journal of Cancer | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | BRAF inhibitors | |
dc.subject | BRAFi | |
dc.subject | MEKi | |
dc.subject | Metastatic melanoma | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Australia | |
dc.subject | Clinical Decision-Making | |
dc.subject | Drug Administration Schedule | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Europe | |
dc.subject | Female | |
dc.subject | Humans | |
dc.subject | Kaplan-Meier Estimate | |
dc.subject | MAP Kinase Kinase Kinases | |
dc.subject | Male | |
dc.subject | Melanoma | |
dc.subject | Middle Aged | |
dc.subject | Proportional Hazards Models | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Proto-Oncogene Proteins B-raf | |
dc.subject | Retrospective Studies | |
dc.subject | Risk Factors | |
dc.subject | Signal Transduction | |
dc.subject | Skin Neoplasms | |
dc.subject | Time Factors | |
dc.subject | Treatment Outcome | |
dc.subject | United States | |
dc.title | Rechallenge with BRAF-directed treatment in metastatic melanoma: A multi-institutional retrospective study. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-12-02 | |
dc.date.updated | 2022-08-30T09:39:24Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.ejca.2017.12.007 | |
rioxxterms.licenseref.startdate | 2018-03-01 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/29360604 | |
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/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.) | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.ejca.2017.12.007 | |
pubs.volume | 91 | |
dc.contributor.icrauthor | Larkin, James | |
icr.provenance | Deposited by Mr Arek Surman on 2022-08-30. Deposit type is initial. No. of files: 1. Files: e000604.full.pdf | |
icr.provenance | Deposited by Mr Arek Surman on 2022-08-30. Deposit type is subsequent. No. of files: 1. Files: 1-s2.0-S0959804917314867-main.pdf | |