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Abstract Details
Comparative efficacy of novel combination strategies for unresectable hepatocellular carcinoma: A network metanalysis of phase III trials
Eur J Cancer. 2022 Oct;174:57-67. doi: 10.1016/j.ejca.2022.06.058.Epub 2022 Aug 12.
1Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120NN, London, UK; Department of Medical Oncology, University Campus Bio-Medico of Rome, Italy.
2Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120NN, London, UK; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy.
3Department of Translational Medicine, Università Del Piemonte Orientale UPO, Via Solaroli 17, 28100, Novara, NO, Italy.
4Marmara University, School of Medicine, Department of Gastroenterology, Istanbul, Turkey.
5Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
6Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120NN, London, UK.
7Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120NN, London, UK; Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy. Electronic address: david.pinato@imperial.ac.uk.
Abstract
Background: Dual programmed cell death-1 and vascular endothelial growth factor pathway inhibition is the novel standard of care for patients with unresectable hepatocellular carcinoma. Direct comparisons between first-line treatments are lacking.
Method: We conducted a literature search in MEDLINE (https://pubmed.ncbi.nlm.nih.gov), the Cochrane library (https://www.cochranelibrary.com) and Embase (www.embase.com) between January 2007 and February 2022. We included phase III randomised controlled trials that tested immune-checkpoint inhibitors or tyrosine kinase inhibitors, including sorafenib, lenvatinib and donafenib, and evaluated as primary end-point overall survival (OS) or progression-free survival (PFS). Studies testing loco-regional therapies were excluded. The primary end-point was to compare the efficacy of first-line options in terms of OS and PFS. We extracted Hazard ratios (HR) and 95% confidence intervals (95% CI) for OS and PFS and performed a frequentist network meta-analysis with fixed effect multivariable meta-regression models. The research protocol was registered in PROSPERO, an international prospective register of systematic reviews (registration code CRD42022312489).
Findings: Literature review yielded 13709 results, after duplicates removal and exclusion of not relevant studies, 70 papers were available for screening. After full-text review, 9 studies were eligible for analysis. Atezolizumab plus bevacizumab reduced the risk of death compared to placebo (HR 0·40; 95% CI 0·28-0·57), sorafenib (HR 0·58; 95% CI 0·42-0·80), lenvatinib (HR 0·63; 95% CI 0·44-0·89), atezolizumab plus cabozantinib (HR 0·64; 95% CI 0·43-0·97), nivolumab (HR 0·68; 95% CI 0·48-0·98) and donafenib (HR 0·69; 95% CI 0·48-0·99). Atezolizumab plus bevacizumab was not statistically superior to durvalumab plus tremelimumab (HR 0·74; 95% CI 0·52-1·06) and sintilimab plus IBI305 (HR 1·02; 95% CI 0·67-1·55) in reducing the risk of death. Efficacy was associated with a higher risk of grade 3 adverse events.