# Relative treatment effects of first-line chemotherapy and immunotherapy for hepatocellular carcinoma: A systematic review and meta-analysis

## TL;DR

This study compares first-line chemotherapy and immunotherapy for liver cancer, finding that immunotherapy may improve progression-free survival but not overall survival.

## Contribution

The study provides a meta-analysis comparing the relative treatment effects of first-line chemotherapy and immunotherapy for hepatocellular carcinoma.

## Key findings

- Immunotherapy showed significantly better progression-free survival than chemotherapy.
- Overall survival trends favored immunotherapy but were not statistically significant.
- High risk of bias in included studies limits the strength of conclusions.

## Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the fourth most common cause of cancer-related mortality worldwide. Despite advances in immunotherapies and targeted treatments for HCC, chemotherapy remains a valuable first-line treatment. However, the efficacy of immunotherapy compared to that of chemotherapy is unknown. This study aimed to provide a comprehensive understanding of the effects of chemotherapy and immunotherapy on survival outcomes, response rates, and adverse effects.

A thorough literature search of multiple electronic databases, including MEDLINE (PubMed), Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov was conducted from each database’s inception to February 2024 to identify randomized controlled trials (RCTs) that compared first-line chemotherapy (doxorubicin, cisplatin, sorafenib, and fluorouracil) with immunotherapy (pembrolizumab nivolumab, and tislelizumab) for advanced HCC. Two reviewers independently identified the studies, obtained relevant information, and assessed the possibility of bias. The hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) were merged using random effects meta-analysis.

Twenty studies with 1183 patients were examined. All studies had a high risk of bias. According to a meta-analysis, immunotherapy was linked to a significantly better PFS than chemotherapy (HR, 1.44, 95% confidence interval [CI], 1.04–2.00, I2 = 32%). OS showed a similar trend, although the difference was not statistically significant (HR, 1.26, 95% CI, 0.96–1.66, I2 = 0%). Sensitivity analysis revealed that immunotherapy continued to improve PFS compared to chemotherapy while having no discernible effect on OS.

First-line immunotherapy may offer PFS advantages over chemotherapy for the treatment of advanced HCC. However, a high risk of bias limits definitive conclusions. Larger, higher-quality RCTs are needed to confirm the potential benefits of OS and minimize bias. Although chemotherapy remains a valuable option in resource-limited settings where access to targeted therapies is restricted, the widespread availability of immunotherapy makes it essential to compare both treatments to determine the most appropriate first-line option for advanced HCC.

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•There is limited evidence to identify optimal subgroups of chemotherapy vs. immunotherapy in hepatocellular carcinoma (HCC) treatment.•Information on the impact of combination strategies on therapy outcomes is limited.•First-line immunotherapy may offer progression-free survival advantages over chemotherapy in advanced HCC.•Larger and higher-quality randomized controlled trials (RCTs) are necessary to confirm potential overall survival advantages.

There is limited evidence to identify optimal subgroups of chemotherapy vs. immunotherapy in hepatocellular carcinoma (HCC) treatment.

Information on the impact of combination strategies on therapy outcomes is limited.

First-line immunotherapy may offer progression-free survival advantages over chemotherapy in advanced HCC.

Larger and higher-quality randomized controlled trials (RCTs) are necessary to confirm potential overall survival advantages.