Intermediate-advanced hepatocellular carcinoma in Argentina:Treatment and survival analysis

BACKGROUND Hepatocellular carcinoma(HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC.AIM To describe real-life treatments performed in patients with intermediateadvanced HCC before the approval of new systemic options.METHODS This longitudinal observational cohort study was conducted between 2009 and2016 in 14 different regional hospitals from Argentina. Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer(BCLC) HCC stages(BCLC B to D). Primary end point analyzed was survival, which was assessed for each BCLC stage from the date of treatment until last patient follow-up or death.Kaplan Meier survival curves and Cox regression analysis were performed, with hazard ratios(HR) calculations and 95% confidence intervals(95%CI).RESULTS From 327 HCC patients, 41% were BCLC stage B, 20% stage C and 39% stage D.Corresponding median survival were 15 mo(IQR 5-26 mo), 5 mo(IQR 2-13 mo)and 3 mo(IQR 1-13 mo)(P < 0.0001), respectively. Among BCLC-B patients(n =135), 57% received TACE with a median number of 2 sessions(IQR 1-3 sessions).Survival was significantly better in BCLC-B patients treated with TACE HR =0.29(CI: 0.21-0.40) than those without TACE. After tumor reassessment by RECIST 1.1 criteria following the first TACE, patients with complete response achieved longer survival (HR = 0.15(CI: 0.04-0.56, P = 0.005))Eighty-two patients were treated with sorafenib, mostly BCLC-B and C(87.8%). However,12.2% were BCLC-D. Median survival with sorafenib was 4.5 mo(IQR 2.3-11.7 mo);which was lower among BCLC-D patients 3.2 mo(IQR 2.0-14.1 mo). A total of 36 BCLC-B patients presented tumor progression after TACE. In these patients,treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE [HR = 0.26(CI: 0.09-0.71);P= 0.013].CONCLUSION In this real setting, our results were lower than expected. This highlights unmet needs in Argentina, prior to the introduction of new treatments for HCC.

Lenvatinib as first-line therapy for recurrent hepatocellular carcinoma after liver transplantation:Is the current evidence applicable to these patients?

Liver transplantation(LT)is one of the leading curative therapies for hepatocellular carcinoma(HCC).Despite recent optimization of transplant selection criteria,including alpha-feto protein,HCC recurrence after LT is still the leading cause of death in these patients.During the last decades,effective systemic treatments for HCC,including tyrosine kinase inhibitors and immunotherapy,have been approved.We describe the clinical scenario of a patient with recurrence of HCC five years after LT,who received lenvatinib as first-line systemic therapy to introduce systemic treatment options in this clinical setting.In this opinion review,we detail first and second-line systemic treatment options,focusing on those feasible for patients with recurrent HCC after LT.Several trials have evaluated new drugs to treat HCC patients in first and secondline therapy,but patients with recurrent HCC after LT have been excluded from these trials.Consequently,most of the evidence comes from observational retrospective studies.Whether tyrosine kinase inhibitors will remain the primary therapeutic approach in these patients,due to a relative contraindication for immunotherapy,may be clarified in the near future.

Sequencing of systemic treatment for hepatocellular carcinoma: Second line competitors

During the last decades,further knowledge of hepatocellular carcinoma(HCC)molecular mechanisms has led to development of effective systemic treatments including tyrosine kinase inhibitors(TKIs)and immunotherapy.In this review,we describe first and second line systemic treatment options for advanced HCC.Several trials have evaluated new drugs for the treatment of HCC patients:In first line,lenvatinib resulted non-inferior to sorafenib and it can be used as alternative,even in the lack of evidence for sequential treatment options in second line after lenvatinib.Recently,atezolizumab plus bevacizumab have shown superiority over sorafenib in first-line.Sorafenib-regorafenib sequential administration in selected patients has opened a new paradigm of treatment in advanced HCC with a life expectancy exceeding two years.Other TKIs for second line treatment include cabozantinib and ramucirumab(specifically for patients with Alpha-fetoprotein values≥400 ng/mL).The combination of TKIs with immunotherapy may represent a big step forward for these patients in the near future.