Efficacy and safety of second-line lenvatinib after progression on immunotherapy in advanced hepatocellular carcinoma: A systematic review and meta-analysis.

Abstract

e16258 Background: Immunotherapy is now the standard first-line therapy for advanced hepatocellular carcinoma (HCC). Although lenvatinib was approved for first-line use, its efficacy after immunotherapy remains unclear. Methods: We systematically searched PubMed, Embase, Web of Science, Scopus, and Cochrane for studies evaluating second-line lenvatinib in advanced HCC following first-line immunotherapy. Random-effects meta-analysis was conducted for overall survival (OS) and progression-free survival (PFS). For studies reporting interquartile ranges (IQR), standard errors were estimated assuming normal distribution. Not-reached OS values were conservatively imputed with 50% increased standard error to reflect uncertainty. Sensitivity analyses were performed for cohorts with ≥50 patients. Results: Of 491 references screened, 9 studies (N = 388) met eligibility. All were retrospective, and 2 were multinational. The pooled median OS was 12.3 months (95% CI 7.39–17.22; I² = 91.1%), and the pooled median PFS was 5.17 months (3.78–6.55; I² = 89.7%). In larger cohorts (n≥50), OS remained consistent at 12.74 months (6.09–19.39; I² = 95.4%), and PFS was 4.56 months (3.89–5.23; I² = 0%). Grade ≥3 adverse events included fatigue (8.9%), elevated transaminases (5.4%), and hypertension (5.3%). Conclusions: Lenvatinib demonstrates meaningful clinical activity and reasonable toxicity profile as a second-line option after immunotherapy in advanced HCC, supporting further prospective validation. Characteristics of included studies and the reported median months of OS and PFS. Authors n OS (95% CI) PFS (95% CI) Qin et al. 50 8.5 (7.5–10.5) 5 (4.5-6.5) Falette-Puisieux et al. 8 9.2 (1.20–9.17) 4.4 (1.87–5.73) Yano et al. 24 21.1 (18.8–NR) 10.5 (8.2–12.1) Hiraoka et al. 101 15.7 (9.6–NR) 4.4 (3.3-5.4) Yoo et al. 19 16.6 (3.6–29.6) 6.1 (1.6-10.5) Persano et al. 84 17.0 (14.8–18.9) Not reported Chon et al. 40 10.3 (6.8–NR) 3.5 (3.0–4.2) Chen et al. 9 Not reported 2.0 Palmer et al. 53 12.8 (6.7–19.5) 3.7 (3.2–6.6)