Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial
- PMID: 26361969
- DOI: 10.1016/S1470-2045(15)00198-9
Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial
Abstract
Background: There is no standard of care for adjuvant therapy for patients with hepatocellular carcinoma. This trial was designed to assess the efficacy and safety of sorafenib versus placebo as adjuvant therapy in patients with hepatocellular carcinoma after surgical resection or local ablation.
Methods: We undertook this phase 3, double-blind, placebo-controlled study of patients with hepatocellular carcinoma with a complete radiological response after surgical resection (n=900) or local ablation (n=214) in 202 sites (hospitals and research centres) in 28 countries. Patients were randomly assigned (1:1) to receive 400 mg oral sorafenib or placebo twice a day, for a maximum of 4 years, according to a block randomisation scheme (block size of four) using an interactive voice-response system. Patients were stratified by curative treatment, geography, Child-Pugh status, and recurrence risk. The primary outcome was recurrence-free survival assessed after database cut-off on Nov 29, 2013. We analysed efficacy in the intention-to-treat population and safety in randomly assigned patients receiving at least one study dose. The final analysis is reported. This study is registered with ClinicalTrials.gov, number NCT00692770.
Findings: We screened 1602 patients between Aug 15, 2008, and Nov 17, 2010, and randomly assigned 1114 patients. Of 556 patients in the sorafenib group, 553 (>99%) received the study treatment and 471 (85%) terminated treatment. Of 558 patients in the placebo group, 554 (99%) received the study treatment and 447 (80%) terminated treatment. Median duration of treatment and mean daily dose were 12·5 months (IQR 2·6-35·8) and 577 mg per day (SD 212·8) for sorafenib, compared with 22·2 months (8·1-38·8) and 778·0 mg per day (79·8) for placebo. Dose modification was reported for 497 (89%) of 559 patients in the sorafenib group and 206 (38%) of 548 patients in the placebo group. At final analysis, 464 recurrence-free survival events had occurred (270 in the placebo group and 194 in the sorafenib group). Median follow-up for recurrence-free survival was 8·5 months (IQR 2·9-19·5) in the sorafenib group and 8·4 months (2·9-19·8) in the placebo group. We noted no difference in median recurrence-free survival between the two groups (33·3 months in the sorafenib group vs 33·7 months in the placebo group; hazard ratio [HR] 0·940; 95% CI 0·780-1·134; one-sided p=0·26). The most common grade 3 or 4 adverse events were hand-foot skin reaction (154 [28%] of 559 patients in the sorafenib group vs four [<1%] of 548 patients in the placebo group) and diarrhoea (36 [6%] vs five [<1%] in the placebo group). Sorafenib-related serious adverse events included hand-foot skin reaction (ten [2%]), abnormal hepatic function (four [<1%]), and fatigue (three [<1%]). There were four (<1%) drug-related deaths in the sorafenib group and two (<1%) in the placebo group.
Interpretation: Our data indicate that sorafenib is not an effective intervention in the adjuvant setting for hepatocellular carcinoma following resection or ablation.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Comment in
-
Adjuvant sorafenib for liver cancer: wrong stage, wrong dose.Lancet Oncol. 2015 Oct;16(13):1279-81. doi: 10.1016/S1470-2045(15)00296-X. Lancet Oncol. 2015. PMID: 26433814 Free PMC article. No abstract available.
-
Sorafenib in adjuvant setting: call for precise and personalized therapy.Transl Gastroenterol Hepatol. 2016 Mar 16;1:13. doi: 10.21037/tgh.2016.03.13. eCollection 2016. Transl Gastroenterol Hepatol. 2016. PMID: 28138580 Free PMC article. No abstract available.
Similar articles
-
Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial.Lancet Oncol. 2017 Dec;18(12):1624-1636. doi: 10.1016/S1470-2045(17)30683-6. Epub 2017 Oct 26. Lancet Oncol. 2017. PMID: 29107679 Clinical Trial.
-
Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial.Lancet Gastroenterol Hepatol. 2017 Aug;2(8):565-575. doi: 10.1016/S2468-1253(17)30156-5. Epub 2017 Jun 23. Lancet Gastroenterol Hepatol. 2017. PMID: 28648803 Clinical Trial.
-
Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial.Lancet Oncol. 2015 Dec;16(16):1691-9. doi: 10.1016/S1470-2045(15)00362-9. Epub 2015 Nov 6. Lancet Oncol. 2015. PMID: 26549589 Clinical Trial.
-
Adverse events affect sorafenib efficacy in patients with recurrent hepatocellular carcinoma after liver transplantation: experience at a single center and review of the literature.Eur J Gastroenterol Hepatol. 2013 Feb;25(2):180-6. doi: 10.1097/MEG.0b013e328359e550. Eur J Gastroenterol Hepatol. 2013. PMID: 23044808 Review.
-
A systematic review of sorafenib in Child-Pugh A patients with unresectable hepatocellular carcinoma.J Clin Gastroenterol. 2013 Nov-Dec;47(10):871-80. doi: 10.1097/MCG.0b013e3182a87cfd. J Clin Gastroenterol. 2013. PMID: 24100749 Review.
Cited by
-
Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma.World J Gastroenterol. 2024 May 21;30(19):2512-2522. doi: 10.3748/wjg.v30.i19.2512. World J Gastroenterol. 2024. PMID: 38817666 Free PMC article. Review.
-
Immunotherapy as a Complement to Surgical Management of Hepatocellular Carcinoma.Cancers (Basel). 2024 May 12;16(10):1852. doi: 10.3390/cancers16101852. Cancers (Basel). 2024. PMID: 38791931 Free PMC article. Review.
-
Insights in Molecular Therapies for Hepatocellular Carcinoma.Cancers (Basel). 2024 May 10;16(10):1831. doi: 10.3390/cancers16101831. Cancers (Basel). 2024. PMID: 38791911 Free PMC article. Review.
-
Identifying symptom clusters and temporal interconnections in patients with lung tumors after CT-guided microwave ablation: A network analysis.Support Care Cancer. 2024 May 23;32(6):377. doi: 10.1007/s00520-024-08560-w. Support Care Cancer. 2024. PMID: 38780815
-
Adjuvant Therapy for Hepatocellular Carcinoma After Curative Treatment: Several Unanswered Questions.J Clin Transl Hepatol. 2024 May 28;12(5):525-533. doi: 10.14218/JCTH.2024.00030. Epub 2024 Apr 24. J Clin Transl Hepatol. 2024. PMID: 38779519 Free PMC article. Review.
Publication types
MeSH terms
Substances
Associated data
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical