A meta-analysis of randomized controlled trials of systemic therapies for hepatocellular carcinoma demonstrated a link between outcomes from checkpoint inhibitor therapy and etiology of liver disease. The results published in Gastroenterology further suggest immunotherapies are potentially less effective against non-viral etiologies
Phase 3 randomized controlled trials across disease stages were reviewed and a meta-analysis conducted to examine the relationship between etiology and outcomes after systemic therapies with either tyrosine-kinase inhibitor/antiangiogenic or immune checkpoint inhibitor therapy.
Between 2002 and 2020, a total of 76 trials were identified and 49 were deemed high quality and included in the analysis. These trials included 22,113 patients receiving adjuvant (n=7) and primary treatment for early (n=2), intermediate (n=7), and advanced stage disease (first-line, n=21; second-line, n=12).
Of these, 9 trials reported positive results and 7 established the accepted drugs for advanced hepatocellular carcinoma: sorafenib, lenvatinib, atezolizumab+bevacizumab, regorafenib, cabozantinib, and ramucirumab. Treatments from 2 early-stage trials have not yet been adopted: adjuvant cytokine-induced killer cells and sorafenib-hepatic arterial infusion with folinic acid, fluorouracil, and oxaliplatin (FOLFOX).
A sub-group analysis of 8 trials involving immune checkpoint inhibiters found they were significantly more effective in patients with viral hepatitis compared with non-viral related hepatocellular carcinoma. There were no observable differences related to etiology in patients treated with tyrosine-kinase inhibitors and anti-vascular endothelial growth factor.
Study limitations included reliance on pooled data rather than individual patient data. Additionally, specific data on nonalcoholic steatohepatitis and alcohol-related hepatocellular carcinoma were not available. Finally, study authors noted heterogeneity among the included trials.
Investigators concluded that ongoing trials of novel combination regimens, including tyrosine-kinase inhibitors plus immunotherapies, are being tested in properly designed and high-quality randomized control trials. “[T]hus results will be instrumental in expanding the landscape of therapies for this highly lethal disease,” they concluded.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Haber PK, Puigvehí M, Castet F, et al. Evidence-based management of HCC: systematic review and meta-analysis of randomized controlled trials (2002-2020). Gastroenterol. Published online June 11, 2021. doi:10.1053/j.gastro.2021.06.008