Outcomes of Sorafenib for Recurrent Hepatocellular Carcinoma After Liver Transplantation in the Era of Combined and Sequential Treatments

Abstract

Background. Sorafenib and other tyrosine kinase inhibitors are the current standard of care for hepatocellular carcinoma (HCC) recurring after liver transplantation (LT). Sorafenib is sometimes regarded as a scarcely effective treatment in this setting because of some studies showing a short overall survival (OS) indirectly compared with historical series of nontransplanted patients. Additional data from multicenter prospective studies are needed before drawing definite conclusions. Methods. Retrospective analyses of a large prospective multicenter dataset of sorafenib-treated HCC patients to report the characteristics and outcomes of LT recipients (n = 81). Results. At the baseline, LT patients had key prognostic features (high prevalence of metastatic disease, and low prevalence of macrovascular invasion, α-fetoprotein >400 ng/mL, ALBI grade >1, performance status >0) that differentiated them from the typical populations of non-LT patient reported in clinical trials and observational studies. Moreover, a relevant proportion of LT patients received concurrent locoregional (12.3%) and postprogression systemic treatments (34.2%), resulting in a median OS of 18.7 mo. Conclusions. Multimodal and sequential treatments are relatively frequent in post-LT HCC patients and contribute to a remarkable OS, together with favorable baseline characteristics. Despite the impossibility of matching with non-LT patients, our results indirectly suggest that the metastatic nature of post-LT recurrence and concurrent antirejection regimens should not discourage systemic treatments.

Prognostic impact of metastatic site in patients receiving first-line sorafenib therapy for advanced hepatocellular carcinoma

“…With these preconditions, TKI monotherapy seems to be outdated, but it still assumes a central role in the therapeutic scenario for patients with advanced HCC and contraindications to ICIs [35] or solid organ recipients [36]; furthermore, recent studies seem to highlight that the etiology of underling liver disease could influence the response to different first-line therapies [37].…”

Pushing the limits of treatment for hepatocellular carcinoma

“…Of the 26 patients who underwent sorafenib treatment followed by LT, 15 were alive without disease recurrence at 5 years. Another recent study found that post-LT patients with progression of HCC who received adjuvant sorafenib had median OS of 18 months, which is considerably improved from previous estimates [36]. Antiangiogenic agents are often used in conjunction with ICIs and have been shown to have reasonably good outcomes with cases of post-LT HCC recurrence [37–40].…”

Recent advances in recurrent hepatocellular carcinoma therapy

“…The incidence of intrahepatic metastasis and multicentric recurrent HCC was 59.4% and 27.5%, respectively, which were accompanied by loss of heterozygosity (63.8%) and microsatellite instability (30.0%) between primary and recurrent tumors[ 34 ]. Concerning previously unidentified circulating tumor cells or preexisting metastasis caused by the current technology that contribute to extrahepatic relapse, metastatic tumor lesions in the graft are originally formed from circulating cells or extrahepatic locales, providing a greater potential for biological advancement[ 35 ].…”

“…Sequential sorafenib treatments are similarly common in recurrent HCC patients following LT. These treatments improve OS compared to non-LT treatments and do not suppress systemic treatments with concurrent antirejection strategy[ 35 ]. Treatment with sorafenib and TACE was associated with a higher 5-year OS and PFS compared to those treated with TACE alone in patients with recurrent intermediate-stage HCC and lesions positive for MVI, but patients with MVI-negative lesions did not show a survival benefit from combined therapy[ 114 ].…”