mRECIST to predict survival in advanced hepatocellular carcinoma: Analysis of two randomised phase II trials comparing nintedanib vs sorafenib
Journal
Liver International
Journal Volume
37
Journal Issue
7
Pages
1047-1055
Date Issued
2017
Author(s)
Abstract
Background & Aims: Response Evaluation Criteria in Solid Tumors (RECIST) has been shown to be a poor surrogate for survival benefit with targeted therapy in advanced hepatocellular carcinoma (HCC). Methods: We investigated whether response evaluated using modified RECIST (mRECIST) predicted overall survival (OS) using data from two Phase II clinical trials. Analyses were conducted on pooled data from 188 patients with advanced HCC treated with nintedanib or sorafenib, of whom 180 were evaluable for response. Cox regression and Kaplan-Meier survival analyses were used to explore differences in OS between the responders and non-responders according to RECIST 1.0 and mRECIST criteria. Multivariate Cox proportional hazards models, including factors known to influence survival, were used to compare survival according to RECIST and mRECIST response. Results: Discordance between RECIST and mRECIST evaluation was most common for assessment of partial response (12.2%) and stable disease (13.3%). OS was significantly longer in patients with response compared to patients without response—RECIST: hazard ratio (HR) 0.325 (95% confidence interval [CI] 0.130-0.815), P=.0122; mRECIST: HR 0.544 (95% CI 0.335-0.881), P=.0122. HRs from the multivariate models used to evaluate response by RECIST or by mRECIST as predictors of OS approached significance for RECIST (0.40 [95% CI 0.16–1.01]; P=.053) and for mRECIST (0.62 [95% CI 0.38–1.01]; P=.053). Conclusions: Response according to RECIST or mRECIST is associated with improved survival and should be considered as a valid endpoint for use in HCC clinical trials. ? 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Subjects
angiogenesis; hepatocellular carcinoma; overall survival
SDGs
Other Subjects
alpha fetoprotein; nintedanib; sorafenib; antineoplastic agent; carbanilamide derivative; indole derivative; nicotinamide; nintedanib; protein kinase inhibitor; sorafenib; adult; advanced cancer; Article; cancer chemotherapy; cancer radiotherapy; cancer staging; cancer survival; chemoembolization; Child Pugh score; controlled study; drug efficacy; drug safety; female; human; liver cell carcinoma; major clinical study; male; maximum tolerated dose; middle aged; multicenter study; overall survival; phase 1 clinical trial; phase 2 clinical trial; prediction; prospective study; radiofrequency ablation; randomized controlled trial; response evaluation criteria in solid tumors; systemic therapy; aged; analogs and derivatives; chi square distribution; clinical trial; comparative study; diagnostic imaging; Kaplan Meier method; liver cell carcinoma; liver tumor; mortality; multivariate analysis; nuclear magnetic resonance imaging; pathology; predictive value; proportional hazards model; risk factor; time factor; very elderly; x-ray computed tomography; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Hepatocellular; Chi-Square Distribution; Female; Humans; Indoles; Kaplan-Meier Estimate; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Multivariate Analysis; Niacinamide; Phenylurea Compounds; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Protein Kinase Inhibitors; Response Evaluation Criteria in Solid Tumors; Risk Factors; Time Factors; Tomography, X-Ray Computed
Publisher
Blackwell Publishing Ltd
Type
journal article