Tim Meyer1, Daniel H Palmer2,3, Ann-Lii Cheng4, Julia Hocke5, Arsène-Bienvenu Loembé6, Chia-Jui Yen7. 1. UCL Cancer Institute, University College London, London, UK. 2. Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. 3. Clatterbridge Cancer Centre, Bebington, UK. 4. National Taiwan University Hospital, Taipei, Taiwan. 5. Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. 6. Boehringer Ingelheim B.V., Alkmaar, the Netherlands. 7. National Cheng Kung University Hospital, Tainan, Taiwan.
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.
RCT Entities:
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.
Authors: Josep M Llovet; Robin Kate Kelley; Augusto Villanueva; Amit G Singal; Eli Pikarsky; Sasan Roayaie; Riccardo Lencioni; Kazuhiko Koike; Jessica Zucman-Rossi; Richard S Finn Journal: Nat Rev Dis Primers Date: 2021-01-21 Impact factor: 52.329
Authors: Angel Alsina; Masatoshi Kudo; Arndt Vogel; Ann-Lii Cheng; Won Young Tak; Baek-Yeol Ryoo; Thomas R Jeffry Evans; Carlos López López; Bruno Daniele; Soamnauth Misir; Min Ren; Namiki Izumi; Shukui Qin; Richard S Finn Journal: Liver Cancer Date: 2019-12-16 Impact factor: 11.740