Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase III STAH trial

Joong Won Park, Yoon Jun Kim, Do Young Kim, Si Hyun Bae, Seung Woon Paik, Youn Jae Lee, Hwi Young Kim, Han Chu Lee, Sang Young Han, Jae Youn Cheong, Oh Sang Kwon, Jong Eun Yeon, Bo Hyun Kim, Jaeseok Hwang

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Abstract

Background & Aims: Sorafenib is first-line standard of care for patients with advanced hepatocellular carcinoma (HCC), yet it confers limited survival benefit. Therefore, we aimed to compare clinical outcomes of sorafenib combined with concurrent conventional transarterial chemoembolization (cTACE) vs. sorafenib alone in patients with advanced HCC. Methods: In this investigator-initiated, multicenter, phase III trial, patients were randomized to receive sorafenib alone (Arm S, n = 169) or in combination with cTACE on demand (Arm C, n = 170). Sorafenib was started within 3 days and cTACE within 7–21 days of randomization. The primary endpoint was overall survival (OS). Results: For Arms C and S, the median OS was 12.8 vs. 10.8 months (hazard ratio [HR] 0.91; 90% CI 0.69–1.21; p = 0.290); median time to progression, 5.3 vs. 3.5 months (HR 0.67; 90% CI 0.53–0.85; p = 0.003); median progression-free survival, 5.2 vs. 3.6 months (HR 0.73; 90% CI 0.59–0.91; p = 0.01); and tumor response rate, 60.6% vs. 47.3% (p = 0.005). For Arms C and S, serious (grade ≥3) adverse events occurred in 33.3% vs. 19.8% (p = 0.006) of patients and included increased alanine aminotransferase levels (20.3% vs. 3.6%), hyperbilirubinemia (11.8% vs. 3.0%), ascites (11.8% vs. 4.2%), thrombocytopenia (7.2% vs. 1.2%), anorexia (7.2% vs. 1.2%), and hand-foot skin reaction (10.5% vs. 11.4%). A post hoc subgroup analysis compared OS in Arm C patients (46.4%) receiving ≥2 cTACE sessions to Arm S patients (18.6 vs. 10.8 months; HR 0.58; 95% CI 0.40–0.82; p = 0.006). Conclusion: Compared with sorafenib alone, sorafenib combined with cTACE did not improve OS in patients with advanced HCC. However, sorafenib combined with cTACE significantly improved time to progression, progression-free survival, and tumor response rate. Sorafenib alone remains the first-line standard of care for patients with advanced HCC. Lay summary: For patients with advanced hepatocellular carcinoma requiring sorafenib therapy, co-administration with conventional transarterial chemoembolization did not improve overall survival compared to sorafenib alone. Therefore, sorafenib alone remains the first-line standard of care for patients with advanced hepatocellular carcinoma. Clinical Trial Number: NCT01829035.

Original languageEnglish
Pages (from-to)684-691
Number of pages8
JournalJournal of Hepatology
Volume70
Issue number4
DOIs
Publication statusPublished - 2019 Apr

All Science Journal Classification (ASJC) codes

  • Hepatology

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    Park, J. W., Kim, Y. J., Kim, D. Y., Bae, S. H., Paik, S. W., Lee, Y. J., Kim, H. Y., Lee, H. C., Han, S. Y., Cheong, J. Y., Kwon, O. S., Yeon, J. E., Kim, B. H., & Hwang, J. (2019). Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase III STAH trial. Journal of Hepatology, 70(4), 684-691. https://doi.org/10.1016/j.jhep.2018.11.029