Early tumor shrinkage and response assessment according to mRECIST predict overall survival in hepatocellular carcinoma patients under sorafenib
Osman Öcal, Regina Schinner, Kerstin Schütte, Enrico N. De Toni, Christian Loewe, Otto van Delden, Vincent Vandecaveye, Bernhard Gebauer, Christoph J. Zech, Christian Sengel, Irene Bargellini, Antonio Gasbarrini, Bruno Sangro, Maciej Pech, Peter Malfertheiner, Jens Ricke, Max Seidensticker, for the SORAMIC study group, E. Kettner, Holger Amthauer, Jarosław B. Ćwikła, Jerzy Walecki, Heinz‐Josef Klümpen, E. Schott, Frank T. Kolligs, Olivier Rosmorduc, Y. Menu, Valériane Leroy, Julia Mayerle, Christoph Trumm, Peter Bartenstein, Maximilian F. Reiser, Thomas Berg, Michael Moche, I. Bilbao, Liebwin Goßner, Peter Reimer, P. Popovič, Borut Štabuc, Piotr Piasecki, Zbigniew Podgajny, Rodolfo Sacco, Markus Peck‐Radosavljevic, Johannes Lämmer, Geert Maleux, Chris Verslype, CA Rosenberg, D. Nitsche, Peter Waldenberger, J. Vergniol, Christophe Cassinotto, Kadir Serkan Yalçın, Bora Peynırcıoğlu, Claudio Zavaglia, Antonio Rampoldi, Albert Tran, P. Chevallier, Rodolphe Anty, Christian Trautwein, Christiane Kühl, Luigi Grazioli, Thomas J. Vogl, Jörg Trojan, Carlo Bartolozzi, Roberto Iezzi, J.-P. Bronowicki, D. Palmer, Joanne Evans, Rishi Sharma, G. K. Weir, Richard Hubner, Bristi Basu, Paul J. Ross
Abstract
BACKGROUND: The aim of this study was to explore the relationship between follow-up imaging characteristics and overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients under sorafenib treatment. METHODS: Associations between OS and objective response (OR) by mRECIST or early tumor shrinkage (ETS; ≥20% reduction in enhancing tumor diameter at the first follow-up imaging) were analyzed in HCC patients treated with sorafenib within a multicenter phase II trial (SORAMIC). 115 patients were included in this substudy. The relationship between survival and OR or ETS were explored. Landmark analyses were performed according to OR at fixed time points. Cox proportional hazards models with OR and ETS as a time-dependent covariate were used to compare survival with factors known to influence OS. RESULTS: The OR rate was 29.5%. Responders had significantly better OS than non-responders (median 30.3 vs. 11.4 months; HR, 0.38 [95% CI, 0.22-0.63], p < 0.001), and longer progression-free survival (PFS; median 10.1 vs. 4.3 months, p = 0.015). Patients with ETS ≥ 20% had longer OS (median 22.1 vs. 11.4 months, p = 0.002) and PFS (median 8.0 vs. 4.3 months, p = 0.034) than patients with ETS < 20%. Besides OR and ETS, male gender, lower bilirubin and ALBI grade were associated with improved OS in univariate analysis. Separate models of multivariable analysis confirmed OR and ETS as independent predictors of OS. CONCLUSION: OR according to mRECIST and ETS in patients receiving sorafenib treatment are independent prognostic factors for OS. These parameters can be used for assessment of treatment benefit and optimal treatment sequencing in patients with advanced HCC.