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dc.contributor.authorDréno, B
dc.contributor.authorRibas, A
dc.contributor.authorLarkin, J
dc.contributor.authorAscierto, PA
dc.contributor.authorHauschild, A
dc.contributor.authorThomas, L
dc.contributor.authorGrob, J-J
dc.contributor.authorKoralek, DO
dc.contributor.authorRooney, I
dc.contributor.authorHsu, JJ
dc.contributor.authorMcKenna, EF
dc.contributor.authorMcArthur, GA
dc.date.accessioned2018-03-02T12:54:32Z
dc.date.issued2017-05
dc.identifier.citationAnnals of oncology : official journal of the European Society for Medical Oncology, 2017, 28 (5), pp. 1137 - 1144
dc.identifier.issn0923-7534
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1473
dc.identifier.eissn1569-8041
dc.identifier.doi10.1093/annonc/mdx040
dc.description.abstractBackground In the coBRIM phase III trial, the addition of cobimetinib, an MEK inhibitor, to vemurafenib, a BRAF inhibitor, significantly improved progression-free survival [hazard ratio (HR), 0.58; P < 0.0001] and overall survival (HR, 0.70; P = 0.005) in advanced BRAF-mutated melanoma. Here, we report on the incidence, course, and management of key adverse events (AEs) in the coBRIM study.Patients and methods Patients were randomly assigned 1:1 to receive vemurafenib (960 mg twice a day) and either cobimetinib (60 mg once a day, 21 days on/7 days off) or placebo. In addition to standard safety evaluations, patients underwent regular ophthalmic, cardiac, and dermatologic surveillance examinations.Results Of 495 patients recruited to the study, 493 patients received treatment and constituted the safety population (cobimetinib combined with vemurafenib, 247; vemurafenib, 246). At data cut-off (30 September 2015), median follow-up was 18.5 months. Nearly every patient experienced an AE. In patients who received cobimetinib combined with vemurafenib, the frequency of grade ≥3 AEs was higher than in patients who received vemurafenib alone (75% versus 61%). Most AEs, including grade ≥3 AEs, occurred within the first treatment cycle. After the first cycle (28 days), the incidence of common AEs (rash, diarrhoea, photosensitivity, elevated creatine phosphokinase, serous retinopathy, pyrexia, and liver laboratory abnormalities) decreased substantially over time. Most AEs were managed conservatively by supportive care measures, dose modifications of study treatment, and, occasionally, permanent treatment discontinuation.Conclusions These data indicate that most AEs arising from treatment with cobimetinib combined with vemurafenib generally occur early in the treatment course, are mild or moderate and are manageable by patient monitoring, dose modification and supportive care.Clinicaltrials.gov NCT01689519.
dc.formatPrint
dc.format.extent1137 - 1144
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectMelanoma
dc.subjectSulfonamides
dc.subjectAzetidines
dc.subjectPiperidines
dc.subjectIndoles
dc.subjectMAP Kinase Kinase Kinases
dc.subjectProto-Oncogene Proteins B-raf
dc.subjectProtein Kinase Inhibitors
dc.subjectDisease-Free Survival
dc.subjectMutation
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectDrug-Related Side Effects and Adverse Reactions
dc.subjectVemurafenib
dc.titleIncidence, course, and management of toxicities associated with cobimetinib in combination with vemurafenib in the coBRIM study.
dc.typeJournal Article
rioxxterms.versionofrecord10.1093/annonc/mdx040
rioxxterms.licenseref.startdate2017-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfAnnals of oncology : official journal of the European Society for Medical Oncology
pubs.issue5
pubs.notesNot 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-statusPublished
pubs.volume28
pubs.embargo.termsNot known
icr.researchteamMelanoma and Kidney Canceren_US
dc.contributor.icrauthorLarkin, Jamesen
dc.contributor.icrauthorMarsden,en


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