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Abstract 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 400 ng/mL (HR 0.70, 95% CI 0.61-0.80, p 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.
Zhang et al. (Fri,) studied this question.