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Purpose <p>The first line palliative treatment medicine contributes modest survival benefit to advanced hepatocellular carcinoma (HCC) patients, but often fails over time. However, the appropriate timing of the second-line therapy initiation remains controversial. This meta-analysis determined the appropriate timing and influencing factors for starting second-line treatment after the failure of first-line therapy.</p> Methods <p>We searched electronic databases including PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials.gov from inception to November 2023. Thirteen studies comprising a total of 5, 449 patients with advanced HCC were included for meta-analysis. The primary outcome of interest was the pooled hazard ratios (HR) of Overall Survival (OS) under different clinical indicators for second-line therapy. The quality assessment was conducted through the Cochrane Risk of Bias tool 2.0. The certainty of evidence was evaluated as GRADE guidelines.</p> Results <p>The meta-analysis revealed that second-line therapy significantly improved OS compared to placebo for patients with progression after first-line therapy (HR 0.89, 95% CI 0.81-0.97, <i>p</i> &lt; 0.05), HBV infection (HR 0.77, 95% CI 0.68-0.86, <i>p</i> &lt; 0.01), extrahepatic spread (HR 0.84, 95% CI 0.73-0.96, <i>p</i> &lt; 0.05), AFP &gt; 400 ng/mL (HR 0.70, 95% CI 0.61-0.80, <i>p</i> &lt; 0.01), and absence of vascular invasion (HR 0.83, 95% CI 0.76–0.90, <i>p</i> &lt; 0.01).</p> Conclusion <p>In cases of first-line treatment failure, patients with progression after first-line therapy, HBV infection, extrahepatic spread, AFP &gt; 400 ng/mL, and absence of vascular invasion are more likely to benefit from second-line therapy. Therefore, timely initiation of second-line therapy is crucial when these indicators are present.</p> Trial registration <p>PROSPERO CRD42022325705.</p>

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Factors influencing the timing of second-line therapy for the treatment of advanced hepatocellular carcinoma: a systematic review and meta-analysis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月20日

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  • Xiaoze Zhang,
  • Fangyuan Zhu,
  • Junsong Wen,
  • Ziwei Pan,
  • Yaodong Zhu

摘要

Purpose

The first line palliative treatment medicine contributes modest survival benefit to advanced hepatocellular carcinoma (HCC) patients, but often fails over time. However, the appropriate timing of the second-line therapy initiation remains controversial. This meta-analysis determined the appropriate timing and influencing factors for starting second-line treatment after the failure of first-line therapy.

Methods

We searched electronic databases including PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials.gov from inception to November 2023. Thirteen studies comprising a total of 5, 449 patients with advanced HCC were included for meta-analysis. The primary outcome of interest was the pooled hazard ratios (HR) of Overall Survival (OS) under different clinical indicators for second-line therapy. The quality assessment was conducted through the Cochrane Risk of Bias tool 2.0. The certainty of evidence was evaluated as GRADE guidelines.

Results

The meta-analysis revealed that second-line therapy significantly improved OS compared to placebo for patients with progression after first-line therapy (HR 0.89, 95% CI 0.81-0.97, p < 0.05), HBV infection (HR 0.77, 95% CI 0.68-0.86, p < 0.01), extrahepatic spread (HR 0.84, 95% CI 0.73-0.96, p < 0.05), AFP > 400 ng/mL (HR 0.70, 95% CI 0.61-0.80, p < 0.01), and absence of vascular invasion (HR 0.83, 95% CI 0.76–0.90, p < 0.01).

Conclusion

In cases of first-line treatment failure, patients with progression after first-line therapy, HBV infection, extrahepatic spread, AFP > 400 ng/mL, and absence of vascular invasion are more likely to benefit from second-line therapy. Therefore, timely initiation of second-line therapy is crucial when these indicators are present.

Trial registration

PROSPERO CRD42022325705.