dc.contributor.author | Zhu, AX | |
dc.contributor.author | Baron, AD | |
dc.contributor.author | Malfertheiner, P | |
dc.contributor.author | Kudo, M | |
dc.contributor.author | Kawazoe, S | |
dc.contributor.author | Pezet, D | |
dc.contributor.author | Weissinger, F | |
dc.contributor.author | Brandi, G | |
dc.contributor.author | Barone, CA | |
dc.contributor.author | Okusaka, T | |
dc.contributor.author | Wada, Y | |
dc.contributor.author | Park, JO | |
dc.contributor.author | Ryoo, B-Y | |
dc.contributor.author | Cho, JY | |
dc.contributor.author | Chung, HC | |
dc.contributor.author | Li, C-P | |
dc.contributor.author | Yen, C-J | |
dc.contributor.author | Lee, K-D | |
dc.contributor.author | Chang, S-C | |
dc.contributor.author | Yang, L | |
dc.contributor.author | Abada, PB | |
dc.contributor.author | Chau, I | |
dc.date.accessioned | 2017-04-13T10:32:58Z | |
dc.date.issued | 2017-02 | |
dc.identifier.citation | JAMA oncology, 2017, 3 (2), pp. 235 - 243 | |
dc.identifier.issn | 2374-2437 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/598 | |
dc.identifier.eissn | 2374-2445 | |
dc.identifier.doi | 10.1001/jamaoncol.2016.4115 | |
dc.description.abstract | Importance REACH is the first phase 3 trial to provide information on hepatocellular cancer (HCC) in the second-line (postsorafenib) setting categorized by Child-Pugh score, a scoring system used to measure the severity of chronic liver disease. This exploratory analysis demonstrates the relationship between a potential ramucirumab survival benefit, severity of liver disease, and baseline α-fetoprotein (αFP).Objective To assess treatment effects and tolerability of ramucirumab by Child-Pugh score in patients with HCC enrolled in the REACH trial.Design, settings, and participants Randomized, double-blind, phase 3 trial of ramucirumab and best supportive care vs placebo and best supportive care as second-line treatment in patients with HCC enrolled between November 4, 2010 and April 18, 2013, from 154 global sites. Overall, 643 patients were randomized and included in this analysis; 565 patients considered Child-Pugh class A (Child-Pugh scores 5 and 6) and 78 patients considered class B (Child-Pugh scores 7 and 8).Interventions Ramucirumab (8 mg/kg) or placebo intravenously plus best supportive care every 2 weeks.Main outcomes and measures Overall survival (OS), defined as time from randomization to death from any cause.Results In the randomized population of 643 patients (mean [SD] age, 62.8 [11.1] years) in this analysis, a potential ramucirumab OS benefit was observed for patients with a Child-Pugh score of 5 (hazard ratio [HR], 0.80; 95% CI, 0.63-1.02; P = .06) but no apparent benefit for patients with Child-Pugh scores of 6 or 7 and 8. In patients with baseline αFP levels of 400 ng/mL (to convert ng/mL to μg/L, multiply by 1.0) or more, a ramucirumab OS benefit was significant for a score of Child-Pugh 5 (HR, 0.61; 95% CI, 0.43-0.87; P = .01) and Child-Pugh 6 (HR, 0.64; 95% CI, 0.42-0.98; P = .04), but was not significant for Child-Pugh 7 and 8. The overall safety profile of ramucirumab, regardless of Child-Pugh score, was considered manageable. Regardless of treatment arm, patients with Child-Pugh scores of 7 and 8 experienced a higher incidence of grade 3 or higher treatment-emergent adverse events, including ascites and asthenia, and special-interest events, including liver injury and/or failure and bleeding, compared with patients with Child-Pugh scores of 5 or 6.Conclusions and relevance In unselected patients, a trend for ramucirumab survival benefit was observed only for patients with a Child-Pugh score of 5. In patients with baseline αFP levels of 400 ng/mL or more, a ramucirumab survival benefit was observed for Child-Pugh scores of 5 and 6. Ramucirumab had a manageable toxic effect profile. These results support the ongoing REACH-2 study of ramucirumab in patients with advanced HCC with underlying Child-Pugh A cirrhosis and baseline αFP levels of 400 ng/mL or more.Trial registration clinicaltrials.gov Identifier: NCT01140347. | |
dc.format | Print | |
dc.format.extent | 235 - 243 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.title | Ramucirumab as Second-Line Treatment in Patients With Advanced Hepatocellular Carcinoma: Analysis of REACH Trial Results by Child-Pugh Score. | |
dc.type | Journal Article | |
rioxxterms.versionofrecord | 10.1001/jamaoncol.2016.4115 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2017-02 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | JAMA oncology | |
pubs.issue | 2 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
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/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 3 | |
pubs.embargo.terms | No embargo | |
dc.contributor.icrauthor | Chau, Ian | en |
dc.contributor.icrauthor | Marsden, | en |