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dc.contributor.authorSeifert, H
dc.contributor.authorFisher, R
dc.contributor.authorMartin-Liberal, J
dc.contributor.authorEdmonds, K
dc.contributor.authorHughes, P
dc.contributor.authorKhabra, K
dc.contributor.authorGore, M
dc.contributor.authorLarkin, J
dc.date.accessioned2017-04-13T09:55:55Z
dc.date.issued2016-04
dc.identifier.citationMelanoma research, 2016, 26 (2), pp. 138 - 144
dc.identifier.issn0960-8931
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/594
dc.identifier.eissn1473-5636
dc.identifier.doi10.1097/cmr.0000000000000218
dc.description.abstractThe BRAF inhibitor vemurafenib is an effective drug in patients with BRAF mutant metastatic melanoma, but resistance occurs after a median of 6 months. The anti-CTLA4-antibody, ipilimumab, is a standard first-line and second-line treatment option in Europe, with a median time to response of 2-3 months, but some patients show rapid clinical deterioration before that. The aim of this analysis was to identify prognostic markers for survival after failure of vemurafenib treatment to identify patients who have a sufficient life expectancy to respond to new immunotherapy treatments. We retrospectively analysed 101 consecutive unselected patients treated with vemurafenib for metastatic melanoma at a single institution. The association between clinical parameters and death within 3 months after cessation of vemurafenib (n=69) was assessed by binary logistic and Cox regression. Of the patients, 45% died within 3 months of progression on vemurafenib. Elevated baseline serum lactate dehydrogenase, absence of normalization of serum lactate dehydrogenase on vemurafenib therapy, performance status of at least 2 at progression and time from primary tumour to metastatic disease less than 5 years were identified as poor prognostic markers. In an exploratory tumour growth kinetics analysis (n=16), we found that following cessation of vemurafenib, approximately a third each showed a stable, decelerated or accelerated rate of tumour growth. Patients with these poor prognostic markers are unlikely to have sufficient life expectancy to complete ipilimumab treatment after failure with vemurafenib. Consideration needs to be given to the elective use of immunotherapy before patients become resistant to vemurafenib. This requires prospective randomized evaluation. Our tumour growth kinetics analysis requires confirmation; however, it may suggest that intermittent vemurafenib treatment should be investigated in clinical trials.
dc.formatPrint
dc.format.extent138 - 144
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectHumans
dc.subjectMelanoma
dc.subjectSkin Neoplasms
dc.subjectDisease Progression
dc.subjectSulfonamides
dc.subjectIndoles
dc.subjectAntineoplastic Agents
dc.subjectPrognosis
dc.subjectImmunotherapy
dc.subjectRetrospective Studies
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectYoung Adult
dc.subjectVemurafenib
dc.titlePrognostic markers and tumour growth kinetics in melanoma patients progressing on vemurafenib.
dc.typeJournal Article
rioxxterms.versionofrecord10.1097/cmr.0000000000000218
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfMelanoma research
pubs.issue2
pubs.notes12 months
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-statusPublished
pubs.volume26en_US
pubs.embargo.terms12 months
icr.researchteamMelanoma and Kidney Canceren_US
dc.contributor.icrauthorGore, Martinen
dc.contributor.icrauthorLarkin, Jamesen


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