ABSTRACT
Background: The efficacy of anti-programmed cell death (PD)-1 monotherapy in advanced hepatocellular carcinoma (aHCC) is limited, and combination therapy with lenvatinib and pembrolizumab has shown promising results. However, comparative studies between immune monotherapies and combination therapies are lacking. Objectives: To investigate the efficacy and safety of anti-PD-1 monotherapy (PD-1) and anti-PD-1 plus lenvatinib (PD-1 + L) in patients with aHCC to guide clinical treatment decisions. Design: A retrospective study was conducted on a cohort of patients with aHCC who received either PD-1 monotherapy or PD-1 + L combination therapy between January 2018 and January 2020. Methods: The study retrospectively reviewed the medical records of 94 eligible patients with aHCC, with 39 in the PD-1 group and 55 in the PD-1 + L group. The efficacy outcomes, including objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety, were assessed. Results: With a median follow-up of 30.1 months, the PD-1 + L group demonstrated a significantly higher ORR (32.7% versus 10.3%, p = 0.013), better DCR (80.0% versus 53.8%, p = 0.012), longer median PFS (10.6 versus 4.4 months, p < 0.001) and longer median OS (18.4 versus 8.5 months, p = 0.013) than PD-1 group. For the responders, the efficacy of the two groups was durable (DOR was 11.6 versus 3.5 months, p = 0.009). Subgroup analyses based on prior tyrosine kinase inhibitor (TKI) treatment and the presence or absence of macrovascular tumor thrombosis or extrahepatic metastases favored the PD-1 + L group. The combination therapy was a good predictor of PFS and OS in multivariate analysis. Grade 3/4 treatment-related adverse events were more common in PD-1 + L group, with higher incidences of hypertension and hand-foot skin reactions. Conclusions: PD-1 monotherapy and PD-1 plus lenvatinib combination therapy were well-tolerated in patients with aHCC. PD-1 + L showed significantly better survival benefits than PD-1 monotherapy.
Understanding the impact of PD-1 and lenvatinib combination therapy on advanced hepatocellular carcinoma Abstract: This plain language summary provides a description of our research on the combination therapy of PD-1 and lenvatinib for advanced Hepatocellular carcinoma (aHCC). We aimed to investigate the effectiveness and safety of this treatment approach and offer insights for clinical decisions. Why was this study done? HCC is a challenging condition to treat, especially in advanced stages. We explored whether the combination of two drugs, PD-1 and lenvatinib, can offer better outcomes for patients with aHCC than PD-1 monotherapy. What did the researchers do? We conducted a retrospective study on patients diagnosed with aHCC who received PD-1 alone or PD-1 combined with lenvatinib between January 2018 and January 2020. We analysed the medical records to assess the treatment's efficacy and safety. What did the researchers find? After a median follow-up of 30.1 months, we observed significant improvements in the combination therapy group, with higher response rates, better disease control, longer progression free survival, and more extended overall survival than those in the PD-1 monotherapy group. Responders in the combination group also experienced a longer duration of response. What do the findings mean? Our results address the lack of data for real-world clinical experiences regarding anti-PD-1 monotherapy for patients with aHCC compared to immunotherapy plus lenvatinib are lacking. The combination of PD-1 and lenvatinib was more effective and offered better survival benefits for patients with aHCC than PD-1 alone. These results could provide new hope for patients with this challenging condition. Limitations: The study was conducted at a single centre with relatively few patients. Additionally, most patients had hepatitis B-associated liver cancer, which may limit the generalisability of our findings to other populations. Conclusions: PD-1 plus lenvatinib is a promising treatment option for patients with aHCC. It is well-tolerated, and its effectiveness surpasses that of PD-1 therapy alone. Our findings could potentially guide clinicians in making treatment decisions for patients with aHCC.
ABSTRACT
Atherosclerosis is characterized as a chronic inflammatory disease and macrophage-derived foam cells play a central role during the pathologic processes. A newly discovered cytokine interleukin-34 (IL-34) is closely associated with various inflammatory and autoimmune diseases. Expression of IL-34 in obesity, inflammatory bowel disease (IBD), rheumatoid arthritis (RA), lupus nephritis and coronary artery diseases (CAD) are significantly elevated. However, the role of IL-34 in atherosclerosis remains unknown. In our present study, we found that IL-34 treatment markedly increased the uptake of oxLDL, intracellular total and esterified cholesterol content but not cholesterol efflux, subsequently promoted foam cell formation through up-regulating CD36 expression via p38 MAPK signal pathway in bone marrow derived macrophages (BMDMs). Furthermore, treatment with IL-34 significantly elevated the oxLDL-induced up-regulation of pro-inflammatory cytokines. Our results conclude that IL-34 facilitates foam cell formation by increasing CD36-mediated lipid uptake and suggest a potential new risk biomarker for atherosclerosis.
