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dc.contributor.authorGershenson, DM
dc.contributor.authorMiller, A
dc.contributor.authorBrady, WE
dc.contributor.authorPaul, J
dc.contributor.authorCarty, K
dc.contributor.authorRodgers, W
dc.contributor.authorMillan, D
dc.contributor.authorColeman, RL
dc.contributor.authorMoore, KN
dc.contributor.authorBanerjee, S
dc.contributor.authorConnolly, K
dc.contributor.authorSecord, AA
dc.contributor.authorO'Malley, DM
dc.contributor.authorDorigo, O
dc.contributor.authorGaillard, S
dc.contributor.authorGabra, H
dc.contributor.authorSlomovitz, B
dc.contributor.authorHanjani, P
dc.contributor.authorFarley, J
dc.contributor.authorChurchman, M
dc.contributor.authorEwing, A
dc.contributor.authorHollis, RL
dc.contributor.authorHerrington, CS
dc.contributor.authorHuang, HQ
dc.contributor.authorWenzel, L
dc.contributor.authorGourley, C
dc.coverage.spatialEngland
dc.date.accessioned2022-07-13T09:22:53Z
dc.date.available2022-07-13T09:22:53Z
dc.date.issued2022-02-05
dc.identifierS0140-6736(21)02175-9
dc.identifier.citationThe Lancet, 2022, 399 (10324), pp. 541 - 553en_US
dc.identifier.issn0140-6736
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5220
dc.identifier.eissn1474-547X
dc.identifier.eissn1474-547X
dc.identifier.doi10.1016/S0140-6736(21)02175-9
dc.identifier.doi10.1016/S0140-6736(21)02175-9
dc.description.abstractBACKGROUND: Low-grade serous carcinoma of the ovary or peritoneum is characterised by MAPK pathway aberrations and its reduced sensitivity to chemotherapy relative to high-grade serous carcinoma. We compared the MEK inhibitor trametinib to physician's choice standard of care in patients with recurrent low-grade serous carcinoma. METHODS: This international, randomised, open-label, multicentre, phase 2/3 trial was done at 84 hospitals in the USA and UK. Eligible patients were aged 18 years or older with recurrent low-grade serous carcinoma and measurable disease, as defined by Response Evaluation Criteria In Solid Tumors version 1.1, had received at least one platinum-based regimen, but not all five standard-of-care drugs, and had received an unlimited number of previous regimens. Patients with serous borderline tumours or tumours containing low-grade serous and high-grade serous carcinoma were excluded. Eligible patients were randomly assigned (1:1) to receive either oral trametinib 2 mg once daily (trametinib group) or one of five standard-of-care treatment options (standard-of-care group): intravenous paclitaxel 80 mg/m2 by body surface area on days 1, 8, and 15 of every 28-day cycle; intravenous pegylated liposomal doxorubicin 40-50 mg/m2 by body surface area once every 4 weeks; intravenous topotecan 4 mg/m2 by body surface area on days 1, 8, and 15 of every 28-day cycle; oral letrozole 2·5 mg once daily; or oral tamoxifen 20 mg twice daily. Randomisation was stratified by geographical region (USA or UK), number of previous regimens (1, 2, or ≥3), performance status (0 or 1), and planned standard-of-care regimen. The primary endpoint was investigator-assessed progression-free survival while receiving randomised therapy, as assessed by imaging at baseline, once every 8 weeks for 15 months, and then once every 3 months thereafter, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02101788, and is active but not recruiting. FINDINGS: Between Feb 27, 2014, and April 10, 2018, 260 patients were enrolled and randomly assigned to the trametinib group (n=130) or the standard-of-care group (n=130). At the primary analysis, there were 217 progression-free survival events (101 [78%] in the trametinib group and 116 [89%] in the standard-of-care group). Median progression-free survival in the trametinib group was 13·0 months (95% CI 9·9-15·0) compared with 7·2 months (5·6-9·9) in the standard-of-care group (hazard ratio 0·48 [95% CI 0·36-0·64]; p<0·0001). The most frequent grade 3 or 4 adverse events in the trametinib group were skin rash (17 [13%] of 128), anaemia (16 [13%]), hypertension (15 [12%]), diarrhoea (13 [10%]), nausea (12 [9%]), and fatigue (ten [8%]). The most frequent grade 3 or 4 adverse events in the standard-of-care group were abdominal pain (22 [17%]), nausea (14 [11%]), anaemia (12 [10%]), and vomiting (ten [8%]). There were no treatment-related deaths. INTERPRETATION: Trametinib represents a new standard-of-care option for patients with recurrent low-grade serous carcinoma. FUNDING: NRG Oncology, Cancer Research UK, Target Ovarian Cancer, and Novartis.
dc.formatPrint
dc.format.extent541 - 553
dc.languageeng
dc.language.isoengen_US
dc.publisherELSEVIER SCIENCE INCen_US
dc.relation.ispartofThe Lancet
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectAdministration, Oral
dc.subjectAdult
dc.subjectAged
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectCarcinoma, Ovarian Epithelial
dc.subjectFemale
dc.subjectHumans
dc.subjectMAP Kinase Kinase 1
dc.subjectMiddle Aged
dc.subjectNeoplasm Grading
dc.subjectNeoplasm Recurrence, Local
dc.subjectOvarian Neoplasms
dc.subjectPaclitaxel
dc.subjectProgression-Free Survival
dc.subjectPyridones
dc.subjectPyrimidinones
dc.subjectStandard of Care
dc.subjectTreatment Outcome
dc.subjectUnited Kingdom
dc.subjectUnited States
dc.titleTrametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial.en_US
dc.typeJournal Article
dcterms.dateAccepted2021-09-21
dc.date.updated2022-07-13T09:22:24Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1016/S0140-6736(21)02175-9en_US
rioxxterms.licenseref.startdate2022-02-05
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/35123694
pubs.issue10324
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume399
dc.contributor.icrauthorBanerjee, Susana
icr.provenanceDeposited by Mr Arek Surman on 2022-07-13. Deposit type is initial. No. of files: 1. Files: Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281LOGS) an international.pdf


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