First‐line sorafenib sequential therapy and liver disease etiology for unresectable hepatocellular carcinoma using inverse probability weighting: A multicenter retrospective study

Abstract

Background and Aims Sequential therapy with molecular‐targeted agents (MTAs) is considered effective for unresectable hepatocellular carcinoma (HCC) patients. This study purposed to evaluate the efficacy of sequential therapy with sorafenib (SORA) as a first‐line therapy and to investigate the therapeutic impact of SORA in nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steato hepatitis (NASH)‐related HCC. Methods We evaluated 504 HCC patients treated with SORA (Study‐1). The times of administration for sorafenib from 2009 to 2015, 2016 to 2017, and 2018 and later were defined as the early‐, mid‐, and late‐term periods, respectively. Among them, 180 HCC patients treated with SORA in addition to MTAs in the mid‐ and late‐term periods were divided into groups based on disease etiology (NAFLD or NASH [n = 37] and viral or alcohol [n = 143]), and outcomes were compared after inverse probability weighting (IPW) (Study‐2). Results Overall survival (OS) of HCC patients who received sequential MTA therapy after first‐line SORA was significantly longer. The median survival times (MST) were 12.6 versus 17.6 versus 17.4 months in the early‐term group, mid‐term group, and the later‐time group (early vs. mid, p = 0.014, early vs. later. p = 0.045), respectively. (Study‐1). In Study‐2, there was no significant differences in OS between the Virus/alcohol group and the NAFLD/NASH group in patients who received sequential therapy (MST was 23.4 and 27.0 months p = 0.173, respectively). The NAFLD or NASH, female sex, albumin‐bilirubin (ALBI) grade 2b, and major Vp (Vp3/Vp4) were significant factors for OS treated with SORA. Conclusions Sequential therapy with SORA as the first‐line treatment improved the prognosis of unresectable HCC patients and was effective regardless of HCC etiology.

Immunotherapy for nonalcoholic fatty liver disease-related hepatocellular carcinoma: Lights and shadows

“…Retrospective studies analyzed the response of tumors to lenvatinib and sorafenib, two TKIs with anti-VEGF activity, associated with the etiology of HCC. While some studies[ 92 - 94 ] did not find significant differences, Shimose et al [ 95 ] reported that NAFLD/NASH etiology was associated with greater survival of the patients treated with sorafenib. This was also confirmed by the REACH-2 trial, which showed that second-line treatment with ramucirumab (an inhibitor of VEGF receptor 2) achieved higher OS in nonviral than in viral HCC patients compared to placebo (HR: 0.633; 95%CI: 0.379–1.057 vs HR: 0.762; 95%CI: 0.435–1.334 vs HR: 0.838; 95%CI: 0.522–1.347, respectively)[ 96 ].…”

“…This was also confirmed by the REACH-2 trial, which showed that second-line treatment with ramucirumab (an inhibitor of VEGF receptor 2) achieved higher OS in nonviral than in viral HCC patients compared to placebo (HR: 0.633; 95%CI: 0.379–1.057 vs HR: 0.762; 95%CI: 0.435–1.334 vs HR: 0.838; 95%CI: 0.522–1.347, respectively)[ 96 ]. However, another study did not find any difference in the OS of patients with NAFLD/NASH who received sequential therapy after sorafenib treatment compared to those with viral or alcohol-related etiology of liver disease[ 95 ]. The favorable effect of angiogenesis inhibition on nonviral HCC was confirmed by administering combination therapies.…”

The m6A/m5C/m1A Regulated Gene Signature Predicts the Prognosis and Correlates With the Immune Status of Hepatocellular Carcinoma

“…Hepatocellular carcinoma (HCC) accounts for approximately 80% of liver cancer (1,2). Recent studies have demonstrated that targeted therapy and immunotherapy significantly affect HCC patient survival (3)(4)(5)(6). For example, Shimose et al reported that sorafenib (SORA) improves overall survival (OS) in HCC patients.…”

“…For example, Shimose et al reported that sorafenib (SORA) improves overall survival (OS) in HCC patients. SORA can improve the prognosis of patients with unresectable HCC as first-line therapy (4). Nonetheless, the prognosis for HCC patients remains unsatisfactory.…”

Differential Response to Sorafenib Administration for Advanced Hepatocellular Carcinoma

“…Albumin-bilirubin (ALBI) grade has been shown to be an indicator of liver dysfunction [ 13 , 14 ]. A combination of ALBI and APRI showed superior predicting power for postoperative hepatic failure [ 15 ].…”