Objective There is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of Trametes robinophila Murr (Huaier granule) to address this unmet need.
Design and results A total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI −12.59 to −2.50; p=0.0018), respectively.
Conclusions This is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group.
Trial registration NCT01770431; Post-results.
- hepatocellular carcinoma
- adjuvant treatment
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QC and CS contributed equally.
Contributors Z-WZ and X-PC were involved in the development of study protocol, study design, data review and interpretation as joint lead investigators of Huaier clinical trial, and both acted as co-lead authors of the Huaier clinical trial report. CS and Z-WZ were both responsible for the provision of patients and data acquisition. QC, ADL and X-PC were responsible for the review of statistical tables, interpretation of data and review of the report for medical consistency against the study database. ADL, YC, B-GP, Z-JZ, J-QC, Y-TD, L-QL, Y-BZ, Q-CZ, G-LX, BL, W-PZ, S-WC, X-YW, HW, X-YP, X-WZ, C-LD, PB, B-CX, Z-RF, L-XL, YM, LZ, Q-SZ, BJ, H-XQ, Y-JW, J-FL, X-HQ and QL were the study physician advisers and contributed to data interpretation. CS and PY were the study statisticians and contributed to data analysis. QC wrote the manuscript. All authors provided critical review of the manuscript and approved the final version for publication.
Funding The study was funded by the Major and Special Program of Hepatic Surgery Clinical Study Center of Hubei Province, China (2014BKB089 and 2013BCB026), the National Natural Science Foundation of China (81471612, 81372495, and 81573262), the Fundamental Research Funds for the Central Universities, HUST (No. 2016YXZD042) and the Twelfth Five-Year Plan for Major and Special Program of the National Science and Technology (2012–2015).
Disclaimer The funders had no role in the study design, data gathering, analysis, interpretation or writing of the report. The corresponding author had full access to all of the study data, and all authors had access upon request. The corresponding authors had final responsibility to submit the manuscript for publication.
Competing interests None declared.
Patient consent Obtained.
Ethics approval The study protocol was approved by Ethics Committee of Tongji Hospital, Tongji Medical College, HUST and all other participating centres. The trial conformed to the ethical guidelines of the Declaration of Helsinki and Good Clinical Practice (GCP) as well as obeyed local laws.
Provenance and peer review Not commissioned; externally peer reviewed.
Correction notice This article has been corrected since it published Online First. The abstract has been corrected.
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