Riccardo Lencioni1, Robert Montal2, Ferran Torres3, Joong-Won Park4, Thomas Decaens5, Jean-Luc Raoul6, Masatoshi Kudo7, Charissa Chang8, José Ríos3, Valerie Boige9, Eric Assenat10, Yoon-Koo Kang11, Ho-Yeong Lim12, Ian Walters13, Josep M Llovet14. 1. Department of Interventional Radiology, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, USA. 2. Liver Cancer Translational Research Laboratory, BCLC Group, IDIBAPS, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Catalonia, Spain. 3. Medical Statistics Core Facility, IDIBAPS, Hospital Clinic, Barcelona, Spain; Biostatistics Unit, Faculty of Medicine, Autonomous University of Barcelona, Barcelona, Spain. 4. Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea. 5. Service d'Hépato-gastro-entérologie, Hôpital Henri Mondor, Faculty of Medicine, University of Paris-Est, and INSERM, Creteil, France. 6. Service d'Oncologie Médicale, Institut Paoli Calmette, Marseille, France. 7. Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan. 8. Liver Cancer Program, Division of Liver Diseases, Ichan School of Medicine at Mount Sinai, New York, NY, USA. 9. Service de Gastro-enterologie, Institut Gustave Roussy, Villejuif, France. 10. Service d'Hépato-gastro-entérologie, Hôpital Saint Eloi, Montpellier Cedex, France. 11. Department of Oncology, Asan Medical Center, Seoul, Republic of Korea. 12. Division of Hematology-Oncology, Samsung Medical Center, Seoul, Republic of Korea. 13. Bristol-Myers Squibb, Wallingford, CT, USA. 14. Liver Cancer Translational Research Laboratory, BCLC Group, IDIBAPS, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Catalonia, Spain; Liver Cancer Program, Division of Liver Diseases, Ichan School of Medicine at Mount Sinai, New York, NY, USA; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain. Electronic address: jmllovet@clinic.cat.
Abstract
BACKGROUND & AIMS: The Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was developed to overcome the limitations of standard RECIST criteria in response assessment of hepatocellular carcinoma (HCC). We aimed to investigate whether objective response by mRECIST accurately predicted overall survival (OS) in patients with advanced HCC treated with systemic targeted therapies and also to preliminarily assess this end-point as a potential surrogate of OS. METHODS: Individual patient data from the BRISK-PS randomized phase III trial comparing brivanib vs. placebo (the first to prospectively incorporate mRECIST) were used to analyze objective response as a predictor of OS in a time-dependent covariate analysis. Patients with available imaging scans during follow-up were included (n=334; 85% of those randomized). Moreover, a correlation of the survival probability in deciles vs. the observed objective response was performed to evaluate its suitability as a surrogate end-point. RESULTS:Objective response was observed in 11.5% and 1.9% of patients treated with brivanib and placebo respectively, and was associated with a better survival (median OS 15.0 vs. 9.4months, p<0.001). In addition, objective response had an independent prognostic value (HR=0.48; 95% confidence interval [CI], 0.26-0.91, p=0.025) along with known prognostic factors. Finally, objective response showed promising results as a surrogate of OS in this trial (R=-0.92; 95% CI, -1 to -0.73, p<0.001). It was an early indicator of the treatment effect (median time to objective response was 1.4months). CONCLUSIONS:Objective response by mRECIST in advanced HCC predicts OS and thus can be considered as a candidate surrogate end-point. Further studies are needed to support this finding. LAY SUMMARY: There is a need to identify surrogate end-points for overall survival in advanced hepatocellular carcinoma. We studied patients from the phase III BRISK trial, comparing brivanib treatment with placebo after sorafenib progression. We demonstrate that objective response is an independent predictor of survival and qualifies as a potential surrogate end-point for overall survival in this patient population. CLINICAL TRIAL NUMBER: NCT00825955.
RCT Entities:
BACKGROUND & AIMS: The Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was developed to overcome the limitations of standard RECIST criteria in response assessment of hepatocellular carcinoma (HCC). We aimed to investigate whether objective response by mRECIST accurately predicted overall survival (OS) in patients with advanced HCC treated with systemic targeted therapies and also to preliminarily assess this end-point as a potential surrogate of OS. METHODS: Individual patient data from the BRISK-PS randomized phase III trial comparing brivanib vs. placebo (the first to prospectively incorporate mRECIST) were used to analyze objective response as a predictor of OS in a time-dependent covariate analysis. Patients with available imaging scans during follow-up were included (n=334; 85% of those randomized). Moreover, a correlation of the survival probability in deciles vs. the observed objective response was performed to evaluate its suitability as a surrogate end-point. RESULTS: Objective response was observed in 11.5% and 1.9% of patients treated with brivanib and placebo respectively, and was associated with a better survival (median OS 15.0 vs. 9.4months, p<0.001). In addition, objective response had an independent prognostic value (HR=0.48; 95% confidence interval [CI], 0.26-0.91, p=0.025) along with known prognostic factors. Finally, objective response showed promising results as a surrogate of OS in this trial (R=-0.92; 95% CI, -1 to -0.73, p<0.001). It was an early indicator of the treatment effect (median time to objective response was 1.4months). CONCLUSIONS: Objective response by mRECIST in advanced HCC predicts OS and thus can be considered as a candidate surrogate end-point. Further studies are needed to support this finding. LAY SUMMARY: There is a need to identify surrogate end-points for overall survival in advanced hepatocellular carcinoma. We studied patients from the phase III BRISK trial, comparing brivanib treatment with placebo after sorafenib progression. We demonstrate that objective response is an independent predictor of survival and qualifies as a potential surrogate end-point for overall survival in this patient population. CLINICAL TRIAL NUMBER: NCT00825955.
Authors: Michael C Wallace; Kenny Sek; Roslyn J Francis; Shaun Samuelson; John Ferguson; Jonathan Tibballs; Ali Asad; David B Preen; Gerry MacQuillan; George Garas; Leon A Adams; Gary P Jeffrey Journal: Dig Dis Sci Date: 2019-08-22 Impact factor: 3.199
Authors: Matthew P Lungren; Alexander J Towbin; Derek J Roebuck; Eric J Monroe; Anne E Gill; Avnesh Thakor; Richard B Towbin; Anne Marie Cahill; C Matthew Hawkins Journal: Pediatr Radiol Date: 2018-01-23