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Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trialстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Bruix Jordi, Qin Shukui, Merle Philippe, Granito Alessandro, Huang Yi-Hsiang, Bodoky György, Pracht Marc, Yokosuka Osamu, Rosmorduc Olivier, Breder Valeriy, Gerolami René, Masi Gianluca, Ross Paul J., Song Tianqiang, Bronowicki Jean-Pierre, Ollivier-Hourmand Isabelle, Kudo Masatoshi, Cheng Ann-Lii, Llovet Josep M., Finn Richard S., LeBerre Marie-Aude, Baumhauer Annette, Meinhardt Gerold, Han Guohong
- Журнал: The Lancet
- Том: 389
- Номер: 10064
- Год издания: 2017
- Издательство: The Lancet Publishing Group
- Местоположение издательства: United Kingdom
- Первая страница: 56
- Последняя страница: 66
- DOI: 10.1016/s0140-6736(16)32453-9
- Аннотация: Background There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose diseaseprogresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients withHCC who have progressed during sorafenib treatment.Methods In this randomised, double-blind, parallel-group, phase 3 trial done at 152 sites in 21 countries, adults withHCC who tolerated sorafenib (≥400 mg/day for ≥20 of last 28 days of treatment), progressed on sorafenib, and hadChild-Pugh A liver function were enrolled. Participants were randomly assigned (2:1) by a computer -generatedrandomisation list and interactive voice response system and stratified by geographical region, Eastern CooperativeOncology Group performance status, macrovascular invasion, extrahepatic disease, and α-fetoprotein level to bestsupportive care plus oral regorafenib 160 mg or placebo once daily during weeks 1–3 of each 4-week cycle. Investigators,patients, and the funder were masked to treatment assignment. The primary endpoint was overall survival (defi ned astime from randomisation to death due to any cause) and analysed by intention to treat. This trial is registered withClinicalTrials.gov, number NCT01774344.Findings Between May 14, 2013, and Dec 31, 2015, 843 patients were screened, of whom 573 were enrolled andrandomised (379 to regorafenib and 194 to placebo; population for efficacy analyses), and 567 initiated treatment(374 received regorafenib and 193 received placebo; population for safety analyses). Regorafenib improved overallsurvival with a hazard ratio of 0·63 (95% CI 0·50–0·79; one-sided p<0·0001); median survival was 10·6 months(95% CI 9·1–12·1) for regorafenib versus 7·8 months (6·3–8·8) for placebo. A dverse events were reported in allregorafenib recipients (374 [100%] of 374) and 179 (93%) of 193 placebo recipients. The most common clinicallyrelevant grade 3 or 4 treatment-emergent events were hypertension (57 patients [15%] in the regorafenib group vsnine patients [5%] in the placebo group), hand–foot skin reaction (47 patients [13%] vs one [1%]), fatigue (34 patients[9%] vs nine patients [5%]), and diarrhoea (12 patients [3%] vs no patients). Of the 88 deaths (grade 5 adverse events)reported during the study (50 patients [13%] assigned to regorafenib and 38 [20%] assigned to placebo), seven (2%)were considered by the investigator to be related to study drug in the regorafenib group and two (1%) in the placebogroup, including two patients (1%) with hepatic failure in the placebo group.Interpretation Regorafenib is the only systemic treatment shown to provide survival benefit in HCC patientsprogressing on sorafenib treatment. Future trials should explore combinations of regorafenib with other systemicagents and third-line treatments for patients who fail or who do not tolerate the sequence of sorafenib andregorafenib
- Добавил в систему: Бредер Валерий Владимирович