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Current Oncology is published by MDPI from Volume 28 Issue 1 (2021). Previous articles were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence, and they are hosted by MDPI on as a courtesy and upon agreement with Multimed Inc..

A Systematic Review and Network Meta-Analysis of Second-Line Therapy in Hepatocellular Carcinoma

by 1, 1, 2, 1,2,3, 1,2,3, 1,2,3,† and 1,2,3,4,*,†
Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada
Department of Medicine, University of Toronto, Toronto, ON, Canada
Canadian Centre for Applied Research in Cancer Control, Toronto, ON, Canada
Author to whom correspondence should be addressed.
Co-senior authors.
Curr. Oncol. 2020, 27(6), 300-306;
Received: 9 September 2020 / Revised: 8 October 2020 / Accepted: 10 November 2020 / Published: 1 December 2020
Background: In patients with advanced hepatocellular carcinoma (HCC) following sorafenib failure, it is unclear which treatment is most efficacious, as treatments in the second-line setting have not been directly compared and no standard therapy exists. This systematic review and network meta-analysis (NMA) aimed to compare the clinical benefits and toxicities of these treatments. Methods: A systematic review of randomized controlled trials (RCTs) was conducted to identify phase iii RCTs in advanced HCC following sorafenib failure. Baseline characteristics and outcomes of placebo were examined for heterogeneity. Primary outcomes of interest were extracted for results, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), grade 3/4 toxicities, and subgroups. An nma was conducted to compare both drugs through the intermediate placebo. Comparisons were expressed as hazard ratios (HRs) for os and PFS, and as risk difference (RD) for ORR and toxicities. Subgroup analyses for OS and PFS were also performed. Results: Two RCTs were identified (1280 patients) and compared through an indirect network; CELESTIAL (cabozantinib vs. placebo) and RESORCE (regorafenib vs. placebo). Baseline characteristics of patients in both trials were similar. Both trials also had similar placebo outcomes. Cabozantinib, compared with regorafenib, showed similar os [hazard ratio (HR): 1.21; 95% confidence interval (CI): 0.90 to 1.62], pfs (HR: 1.02; 95% ci: 0.78 to 1.34) and ORR (−3.0%; 95% ci: −7.6% to 1.7%). Both treatments showed similar toxicities, but there were marginally higher risks of grade 3/4 hand–foot syndrome (5%; 95% ci: 0.1% to 9.8%), diarrhea (4.8%; 95% ci: 1.1% to 8.5%), and anorexia (4.4%; 95% ci: 0.8% to 8.0%) for cabozantinib. Subgroup results for os and pfs were consistent with overall results. Conclusions: Overall, this nma determined that cabozantinib and regorafenib have similar clinical benefits and toxicities for second-line HCC.
Keywords: liver cancer; regorafenib; cabozantinib; sorafenib liver cancer; regorafenib; cabozantinib; sorafenib
MDPI and ACS Style

Santos, S.D.; Udayakumar, S.; Nguyen, A.; Ko, Y.J.; Berry, S.; Doherty, M.; Chan, K.K.W. A Systematic Review and Network Meta-Analysis of Second-Line Therapy in Hepatocellular Carcinoma. Curr. Oncol. 2020, 27, 300-306.

AMA Style

Santos SD, Udayakumar S, Nguyen A, Ko YJ, Berry S, Doherty M, Chan KKW. A Systematic Review and Network Meta-Analysis of Second-Line Therapy in Hepatocellular Carcinoma. Current Oncology. 2020; 27(6):300-306.

Chicago/Turabian Style

Santos, S. Delos, S. Udayakumar, A. Nguyen, Y.J. Ko, S. Berry, M. Doherty, and K.K.W. Chan 2020. "A Systematic Review and Network Meta-Analysis of Second-Line Therapy in Hepatocellular Carcinoma" Current Oncology 27, no. 6: 300-306.

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