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Title: Objective response by mRECIST as a predictor and potential surrogate end point of overall survival in advanced HCC
Author: Lencioni, Riccardo
Montal, Robert
Torre, Ferran
Park, Joong-Won
Decaens, Thomas
Raoul, Jean-Luc
Kudo, Masatoshi
Chang, Charissa Y.
Rios, José
Boige, Valerie
Assenat, Eric
Kang, Yoon-Koo
Lim, Ho-Yeong
Walters, Ian
Llovet i Bayer, Josep Maria
Keywords: Càncer de fetge
Assaigs clínics
Pronòstic mèdic
Liver cancer
Clinical trials
Issue Date: 25-Jan-2017
Publisher: Elsevier
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 endpoint 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. 9.4 months, 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 1.4 months).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.
Note: Versió postprint del document publicat a:
It is part of: Journal of Hepatology, 2017, vol. 66, num. 6, p. 1166-1172
Related resource:
ISSN: 0168-8278
Appears in Collections:Articles publicats en revistes (Medicina)
Publicacions de projectes de recerca finançats per la UE
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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