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. 2021 Mar 31:11:654020.
doi: 10.3389/fonc.2021.654020. eCollection 2021.

Efficacy of First Line Systemic Chemotherapy and Multikinase Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis

Songporn Oranratnachai  1   2 , Sasivimol Rattanasiri  1 , Anantaporn Pooprasert  3 , Amarit Tansawet  1   4 , Thanyanan Reungwetwattana  5 , John Attia  6 , Ammarin Thakkinstian  1
Affiliations

Efficacy of First Line Systemic Chemotherapy and Multikinase Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis

Songporn Oranratnachai et al. Front Oncol. .

Abstract

Background: Hepatocellular carcinoma (HCC) is the third most fatal cancer, with a 5-year survival rate of 18%. Standard frontline-therapy is multikinase inhibitors (MKIs), but accessibility is still limited, particularly in developing countries. This network meta-analysis (NMA) aimed to compare the efficacy of usual chemotherapy vs MKIs.

Method: Randomised-controlled trials (RCTs) comparing any among chemotherapy vs MKIs in treatment-naïve patients with advanced HCCs were identified from MEDLINE and SCOPUS databases. Overall survival (OS) and progression-free survival (PFS) probabilities and times were extracted from Kaplan-Meier curves using Digitizer, and then converted to individual patient time-to-event data. A one-stage mixed-effect survival model was applied to estimate median OS and PFS. A two-stage NMA was applied for the overall response rate and adverse events (AEs) outcome.

Results: A total of 20 RCTs were eligible for NMA. Lenvatinib was the best treatment among single MKIs, with median OS and PFS of 9 and 6.3 months, without significant differences in AEs relative to other MKIs. Median OS and PFS were 0.70 (-0.42, 1.83) and 2.17 (1.41, 2.93) months longer with Lenvatinib than Sorafenib. Among chemotherapy agents, FOLFOX4 had the longest median OS and PFS at 7.9 and 4.3 months, respectively, without significant AEs compared to other chemotherapies. The combination of Sorafenib+Doxorubicin prolonged median OS and PFS to 12.7 and 6.3 months, respectively.

Conclusion: Use of the MKIs Lenvatinib or Sorafenib as first line systemic treatment for advanced HCC could be beneficial. However, FOLFOX4 might be the optimal choice in a developing country where the health-care budget is limited.

Keywords: chemotherapy; first-line systemic treatment; hepatocellular carcinoma; multikinase inhibitors; network meta-analysis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flow diagram.
Figure 2
Figure 2
Risk of bias assessment.
Figure 3
Figure 3
Network map for each outcome. (A – overall survival, B – progression-free survival, C – overall response rate, and D – adverse events).
Figure 4
Figure 4
Risk of adverse events and benefit of overall survival assessment. (A – between Lenvatinib and Sorafenib, B – between FOLFOX4 and Sorafenib).
See this image and copyright information in PMC

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