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

Research output: Contribution to journalArticle

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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

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Hepatocellular Carcinoma
Arm
Survival
Standard of Care
Disease-Free Survival
sorafenib
Hyperbilirubinemia
Anorexia
Random Allocation
Alanine Transaminase
Ascites
Thrombocytopenia
Foot
Neoplasms
Hand
Research Personnel
Clinical Trials
Skin

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Park, Joong Won ; Kim, Yoon Jun ; Kim, Do Young ; Bae, Si Hyun ; Paik, Seung Woon ; Lee, Youn Jae ; Kim, Hwi Young ; Lee, Han Chu ; Han, Sang Young ; Cheong, Jae Youn ; Kwon, Oh Sang ; Yeon, Jong Eun ; Kim, Bo Hyun ; Hwang, Jaeseok. / Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma : The phase III STAH trial. In: Journal of Hepatology. 2019 ; Vol. 70, No. 4. pp. 684-691.
@article{33f0e95554a1481dafc90cf61445b407,
title = "Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase III STAH trial",
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.",
author = "Park, {Joong Won} and Kim, {Yoon Jun} and Kim, {Do Young} and Bae, {Si Hyun} and Paik, {Seung Woon} and Lee, {Youn Jae} and Kim, {Hwi Young} and Lee, {Han Chu} and Han, {Sang Young} and Cheong, {Jae Youn} and Kwon, {Oh Sang} and Yeon, {Jong Eun} and Kim, {Bo Hyun} and Jaeseok Hwang",
year = "2019",
month = "4",
doi = "10.1016/j.jhep.2018.11.029",
language = "English",
volume = "70",
pages = "684--691",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier",
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}

Park, JW, Kim, YJ, Kim, DY, Bae, SH, Paik, SW, Lee, YJ, Kim, HY, Lee, HC, Han, SY, Cheong, JY, Kwon, OS, Yeon, JE, Kim, BH & Hwang, J 2019, 'Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase III STAH trial', Journal of Hepatology, vol. 70, no. 4, pp. 684-691. https://doi.org/10.1016/j.jhep.2018.11.029

Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma : The phase III STAH trial. / Park, Joong Won; Kim, Yoon Jun; Kim, Do Young; Bae, Si Hyun; Paik, Seung Woon; Lee, Youn Jae; Kim, Hwi Young; Lee, Han Chu; Han, Sang Young; Cheong, Jae Youn; Kwon, Oh Sang; Yeon, Jong Eun; Kim, Bo Hyun; Hwang, Jaeseok.

In: Journal of Hepatology, Vol. 70, No. 4, 04.2019, p. 684-691.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma

T2 - The phase III STAH trial

AU - Park, Joong Won

AU - Kim, Yoon Jun

AU - Kim, Do Young

AU - Bae, Si Hyun

AU - Paik, Seung Woon

AU - Lee, Youn Jae

AU - Kim, Hwi Young

AU - Lee, Han Chu

AU - Han, Sang Young

AU - Cheong, Jae Youn

AU - Kwon, Oh Sang

AU - Yeon, Jong Eun

AU - Kim, Bo Hyun

AU - Hwang, Jaeseok

PY - 2019/4

Y1 - 2019/4

N2 - 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.

AB - 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.

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