Robin Park, 1 Laercio Lopes da Silva, 1 Voravech Nissaisorakarn, 1 Ivy Riano, 1 Stephen Williamson, 2 Weijing Sun, 2 Anwaar Saeed2
1 Department of Medicine, MetroWest Medical Center / Tufts University Medical School, Framingham, MA, USA; 2Department of Medicine, Department of Medical Oncology, University of Kansas Cancer Center, Kansas City, KS, USA
Correspondence: Anwaar Saeed
University of Kansas Cancer Center, GI Oncology Program, Kansas City, KS, USA
Background: Several systemic agents have been approved for use in advanced hepatocellular carcinoma (aHCC). However, it is unclear which treatment is superior in the first- or second-line setting due to the lack of head-to-head comparative studies. Therefore, we performed a systematic review and network meta-analysis for the indirect comparison of the systemic agents in the first and second row settings.
Methods: Randomized clinical trials evaluating systemic agents in the first- and second-line environment in aHCC from early to April 2020 were carried out by searching the PubMed, EMBASE and Cochrane databases as well as the annual ASCO and ESMO conferences from 2017 to 2020 Identified survival (OS), progression-free survival (PFS), and objective response rate (ORR) were included. The primary results of interest were pooled hazard ratios (HR) of OS and pooled odds ratios (OR) of ORR in first-line studies and pooled HR of PFS and OR of ORR for second-line studies. In addition, the OS for second-line agents was specified in the qualitative analysis.
Results: In total, studies in the first line comprised 8,335 patients (13 studies) and studies in the second line comprised 4,612 patients (11 studies). In the first line, atezolizumab plus bevacizumab was associated with the highest OS benefit compared to sorafenib (HR 0.58, 95% CI, 0.42–0.80; P-score 0.993). In addition, lenvatinib was associated with the greatest ORR benefit in the first row (OR 3.34, 95% CI, 2.17–5.14; P-score 0.080). On the second line, cabozantinib had the highest PFS benefit versus placebo (HR 0.44, 95% CI, 0.29-0.66; P-score 0.854) and the highest ORR benefit (OR 9.40, 95 % CI, 1.25-) associated. 70.83, P-Score, 0.266).
Conclusion: Atezolizumab plus bevacizumab appears to have superior efficacy among first-line agents, while cabozantinib appears to be superior in the second-line setting. Further studies are needed to determine whether the type of therapy received previously affects the effectiveness of subsequent second-line therapy.
Keywords: advanced hepatocellular carcinoma, targeted therapy, immunotherapy, systemic therapy