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Sequential Treatment of Sorafenib–Regorafenib Versus Sorafenib–Physician’s Choice: A Propensity Score-Matched Analysis

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A Correction to this article was published on 18 March 2021

This article has been updated



Regorafenib has been shown to improve clinical outcomes compared to placebo, becoming a standard second-line therapy for sorafenib-progressed and -tolerated hepatocellular carcinoma (HCC) patients.


We performed a multicentre, retrospective study in Italy and Korea to evaluate the effectiveness of the treatment sequence sorafenib–regorafenib compared with sorafenib and physician’s choice in a real-life setting.

Patients and Methods

A propensity score model was developed to control the results for baseline variable imbalances between the arm treated with sorafenib and regorafenib (S–R) and the arm treated with sorafenib and physician’s choice (S–P). Survival analysis was conducted on the matched population.


After the application of propensity score matching, we analysed 99 patients in the arm treated with S–R and 99 patients in the arm treated with S–P. For the S–R group, the median overall survival was 22.2 months (95% CI 17.1–27.4), compared to 17.9 months (95% CI 15.1–50.0) for the S–P group. The results of the univariate analysis showed a 31% reduction of death risk for patients treated with S–R (p = 0.0382) compared to patients treated with S–P. Interaction tests highlighted the predictive role of alpha-fetoprotein (AFP), neutrophil-to-lymphocyte ratio (NLR), and extrahepatic spread.


This study provides additional proof of the superiority of the S–R treatment over the S–P treatment approach in advanced HCC patients from a real-life setting.

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Authors and Affiliations


Corresponding author

Correspondence to Andrea Casadei-Gardini.

Ethics declarations


No external funding was used in the preparation of this article.

Data availability

The dataset used during the current study is available from the corresponding author on reasonable request.

Conflict of interest

Andrea Casadei Gardini reports receiving consulting fees from AstraZeneca, Bayer, Eisai, MSD, Ipsen, IQVIA, lectures fees from Eisai, Ipsen, Merck Serono, Roche. Changhoon Yoo reports honoraria from BMS, MSD, Bayer, Eisai, Ipsen, AstraZeneca, and Servier, and research grants from Bayer, Ono, AstraZeneca and Servier. Yeonghak Bang, Sara Lonardi, Hyung-Don Kim, Caterina Vivaldi, Margherita Rimini, Giovanni Luca Frassineti, Sook Ryun Park, Mario Domenico Rizzato, Min-Hee Ryu, Francesca Salani, Ilario Giovanni Rapposelli, Baek-Yeol Ryoo, Zagonel Vittorina, Valentina Massa, Martina Valgiusti, Valentina Burgio, Mario Scartozzi andStefano Cascinu declare that they have no conflicts of interest that might be relevant to the contents of this article.

Ethics approval and consent to participate

All patients who participated in the study gave informed consent. The National Data Inspectorate and the Regional Committee for Medical Research Ethics approved the study. The study was performed in accordance with the Declaration of Helsinki.

Author contributions

Conception and design: ACG, YC. Development of methodology and acquired data: all authors. Statistical analysis and interpretation of data: ACG, YC. Writing, review and revision of the paper: all authors. Approved the final version: all authors. Agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: all authors.

Additional information

The original article has been update: Due to affiliation update.

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Bang, Y., Yoo, C., Lonardi, S. et al. Sequential Treatment of Sorafenib–Regorafenib Versus Sorafenib–Physician’s Choice: A Propensity Score-Matched Analysis. Targ Oncol 16, 401–410 (2021).

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