e16152 Background: To assess the efficacy and safety of lenvatinib plus anti-PD-1 versus lenvatinib alone in patients with unresectable hepatocellular carcinoma (u-HCC) and explore the characteristics of the benefit population for combination therapy. Methods: This retrospective study included 70 u-HCC patients that were treated with lenvatinib plus anti-PD-1 and 140 patients treated with lenvatinib alone in Fifth Medical Center of Chinese PLA General Hospital and Electric Power Hospital of Beijing from November 2017 to February 2021. Clinical features were balanced by stabilized inverse probability of treatment weighting (SIPTW). The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Subpopulation treatment effect pattern plot (STEPP) revealed differential treatment effects. The safety was evaluated by Common Terminology Criteria for AEs version 5.0. Results: During the median follow-up of 21.6 months, 120 (57%) patients died. The combination group showed better OS (21.4 vs. 14 months, p = 0.041), PFS (8.0 vs. 6.3 months, p = 0.015), ORR (38.6% vs. 22.9%, p = 0.026), and DCR (85.7% vs. 69.3%, p = 0.016) than the monotherapy group in unadjusted cohort, which was similar to SIPTW adjusted cohort. The two groups had comparable and manageable AEs. Macrovascular invasion (MVI, HR 2.6, 95%CI 2.18 - 3.92), extrahepatic spread (EHS, HR 2.16, 95%CI 1.49 - 3.13), and Child-Pugh B (CPB, HR 2.08, 95%CI 1.45 - 2.99) were independent factors of OS. Combination therapy improved the 12-month survival rate by 38% for patients with MVI or EHS and CPB, and by up to 18% in the other population. Conclusions: In conclusion, lenvatinib plus anti-PD-1 showed a favorable efficacy and controllable safety for u-HCC patients in real-world practice. The absolute improvement of the 12-month survival rate with combination therapy was more substantial in patients with major vascular invasion or extrahepatic spread and Child-Pugh B.

Background We explore the dose–efficacy relationship of lenvatinib plus anti-PD-1 in patients with unresectable hepatocellular carcinoma (u-HCC) infected with hepatitis B virus (HBV) in real-world practice. Furthermore, we identify the population sensitive to lenvatinib plus anti-PD-1 treatments. Methods This retrospective study included 70 patients treated with lenvatinib plus at least 3 cycles of anti-PD-1 and 140 with lenvatinib alone. Stabilized inverse probability of treatment weighting (SIPTW) was used to balance clinical features between the two groups. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed. Subpopulation treatment effect pattern plot (STEPP) estimated treatment-effect differences between the two groups. Results The median age was 54 years, and 189 (90%) cases were male. A total of 180 (85%) patients were infected with HBV. A slowly increasing 12-month survival rate was with the cycles of anti-PD-1, and 5 cycles and more of anti-PD-1 appeared the most beneficial and stable survival rate. The lenvatinib plus at least 3 cycles anti-PD-1 group had better OS (21.4 vs 14 months, p = 0.041), PFS (8.0 vs 6.3 months, p = 0.015) than the lenvatinib alone group in unadjusted cohorts, and the SIPTW adjusted cohorts had confirmed it. For patients with portal vein trunk invasion (PVTI) or extrahepatic spread (EHS) combined with Child-Pugh class B (CPB), lenvatinib plus anti-PD-1 made the 12-month survival rate increase by 38%, while, in the other population, it did only 18%. The two groups had similar AEs (p ≥ 0.05). Conclusion The lenvatinib combined with at least 3 cycles of anti-PD-1 was efficacy and safe for u-HCC patients infected with HBV. Especially, patients with PVTI or EHS combined with CPB may benefit most from the combination therapy.

ScopeApigenin (AP) has many pharmacological activities, including anti‐inflammation, hyperlipidemia‐lowering, and so on. Previous studies show that AP can reduce lipid accumulation in adipocytes in vitro. However, it remains unclear whether and how AP can promote fat‐browning. Therefore, mouse obesity model and preadipocyte induction model in vitro are used to investigate the effects of AP on glycolipid metabolism, browning and autophagy as well as the possible mechanisms.Methods and resultsThe obese mice are intragastrically administrated with AP (0.1 mg g−1 d−1) for 4 weeks; meanwhile, the differentiating preadipocytes are respectively treated with the indicated concentrations of AP for 48 h. Metabolic phenotype, lipid accumulation, and fat‐browning are respectively evaluated by morphological, functional, and specific markers analysis. The results show that AP treatment alleviates the body weight, glycolipid metabolic disorder, and insulin resistance in the obese mice , which is contributed to the pro‐browning effects of AP in vivo and in vitro. Moreover, the study finds that the pro‐browning effect of AP is accomplished through autophagy inhibition mediated by the activation of PI3K‐Akt‐mTOR pathway.ConclusionsThe findings highlight that autophagy inhibition promotes the browning of white adipocytes and suggest that AP would prevent and treat obesity and the associated metabolic disorders.