Show simple item record

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.identifier.citationThe Lancet, 2022, 399 (10324), pp. 541 - 553en_US
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, 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.format.extent541 - 553
dc.relation.ispartofThe Lancet
dc.subjectAdministration, Oral
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectCarcinoma, Ovarian Epithelial
dc.subjectMAP Kinase Kinase 1
dc.subjectMiddle Aged
dc.subjectNeoplasm Grading
dc.subjectNeoplasm Recurrence, Local
dc.subjectOvarian Neoplasms
dc.subjectProgression-Free Survival
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
rioxxterms.typeJournal Article/Reviewen_US
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
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

Files in this item


This item appears in the following collection(s)

Show simple item record
Except where otherwise noted, this item's license is described as