dc.contributor.author | Gershenson, DM | |
dc.contributor.author | Miller, A | |
dc.contributor.author | Brady, WE | |
dc.contributor.author | Paul, J | |
dc.contributor.author | Carty, K | |
dc.contributor.author | Rodgers, W | |
dc.contributor.author | Millan, D | |
dc.contributor.author | Coleman, RL | |
dc.contributor.author | Moore, KN | |
dc.contributor.author | Banerjee, S | |
dc.contributor.author | Connolly, K | |
dc.contributor.author | Secord, AA | |
dc.contributor.author | O'Malley, DM | |
dc.contributor.author | Dorigo, O | |
dc.contributor.author | Gaillard, S | |
dc.contributor.author | Gabra, H | |
dc.contributor.author | Slomovitz, B | |
dc.contributor.author | Hanjani, P | |
dc.contributor.author | Farley, J | |
dc.contributor.author | Churchman, M | |
dc.contributor.author | Ewing, A | |
dc.contributor.author | Hollis, RL | |
dc.contributor.author | Herrington, CS | |
dc.contributor.author | Huang, HQ | |
dc.contributor.author | Wenzel, L | |
dc.contributor.author | Gourley, C | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-07-13T09:22:53Z | |
dc.date.available | 2022-07-13T09:22:53Z | |
dc.date.issued | 2022-02-05 | |
dc.identifier | S0140-6736(21)02175-9 | |
dc.identifier.citation | The Lancet, 2022, 399 (10324), pp. 541 - 553 | en_US |
dc.identifier.issn | 0140-6736 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5220 | |
dc.identifier.eissn | 1474-547X | |
dc.identifier.eissn | 1474-547X | |
dc.identifier.doi | 10.1016/S0140-6736(21)02175-9 | |
dc.description.abstract | BACKGROUND: 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.format | Print | |
dc.format.extent | 541 - 553 | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | ELSEVIER SCIENCE INC | en_US |
dc.relation.ispartof | The Lancet | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Administration, Oral | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Carcinoma, Ovarian Epithelial | |
dc.subject | Female | |
dc.subject | Humans | |
dc.subject | MAP Kinase Kinase 1 | |
dc.subject | Middle Aged | |
dc.subject | Neoplasm Grading | |
dc.subject | Neoplasm Recurrence, Local | |
dc.subject | Ovarian Neoplasms | |
dc.subject | Paclitaxel | |
dc.subject | Progression-Free Survival | |
dc.subject | Pyridones | |
dc.subject | Pyrimidinones | |
dc.subject | Standard of Care | |
dc.subject | Treatment Outcome | |
dc.subject | United Kingdom | |
dc.subject | United States | |
dc.title | Trametinib 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.type | Journal Article | |
dcterms.dateAccepted | 2021-09-21 | |
dc.date.updated | 2022-07-13T09:22:24Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1016/S0140-6736(21)02175-9 | en_US |
rioxxterms.licenseref.startdate | 2022-02-05 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35123694 | |
pubs.issue | 10324 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 399 | |
dc.contributor.icrauthor | Banerjee, Susana | |
icr.provenance | Deposited 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 | |