The clinical significance of sarcopenia in patients with hepatocellular carcinoma treated with lenvatinib and PD-1 inhibitors

• Published in: Frontiers in immunology Vol. 15; p. 1380477
• Main Authors: Sun, Wei, Yin, Xue, Liu, Xiaomin, Wei, Jianying, Yu, Minghua, Li, Wendong, Ding, Xiaoyan, Chen, Jinglong
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 18.04.2024
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - mortality; Clinical Relevance; Female; HCC; Humans; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Immunology; lenvatinib; Liver Neoplasms - drug therapy; Liver Neoplasms - mortality; Male; Middle Aged; PD-1 inhibitor; Phenylurea Compounds - administration & dosage; Phenylurea Compounds - adverse effects; Phenylurea Compounds - therapeutic use; Prognosis; psoas muscle index; Quinolines - adverse effects; Quinolines - therapeutic use; Retrospective Studies; sarcopenia; Sarcopenia - drug therapy; Sarcopenia - etiology; HCC; PD-1 inhibitor; psoas muscle index; lenvatinib; sarcopenia
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1380477

Sarcopenia has gained considerable attention in the context of hepatocellular carcinoma, as it has been correlated with a poorer prognosis among patients undergoing sorafenib or lenvatinib treatment for hepatocellular carcinoma (HCC). The clinical significance of sarcopenia in first-line advanced HCC patients treated with lenvatinib and programmed death-1 (PD-1) inhibitors needs to be clarified. Sarcopenia was diagnosed using CT (Computed tomography) or MRI (Magnetic Resonance Imaging), with the psoas muscle index (PMI) as the surrogate marker. Patients were grouped based on sarcopenia presences, and a comparative analysis examined characteristics, adverse events, and prognosis. The Cox regression analysis was applied to identify independent prognostic factors for survival, while nomograms were constructed to predict 1-year survival. Among 180 patients, 46 had sarcopenia. Patients with baseline sarcopenia demonstrated significantly inferior median progression-free survival (mPFS) (3.0 vs. 8.3 months) and median overall survival (mOS) (7.3 vs. 21.6 months). The same results for mPFS (3.3 vs. 9.2 months) and mOS (9.4 vs. 24.2 months) were observed in patients who developed sarcopenia after treatment. Furthermore, significantly higher grade 3 or higher adverse events (AEs) (73.91% vs 41.79%, p<0.001) were recorded in the sarcopenia group compared to the non-sarcopenia group. In the multivariate analysis, distant metastasis, elevated PLR and CRP levels, and low PMI remained independent predictive factors for poor OS. Additionally, skeletal muscle loss remained a significant independent risk factor for PFS. We developed a nomogram incorporating these four indicators, which predicted 12-month survival with a C-index of 0.853 (95% CI, 0.791 - 0.915), aligning well with actual observations. The prognosis of patients with HCC and sarcopenia is significantly worse when treated with lenvatinib and PD-1 inhibitors. The combination regimen of lenvatinib plus PD-1 inhibitors should be cautiously recommended due to the inferior prognosis and higher AEs.