RESUMEN
Hepatocellular carcinoma (HCC) represents the fourth most common cause of cancer-related death. Surgery, local ablative therapies and liver transplantation are the only potentially curative strategies, but the majority of patients present with advanced disease at diagnosis or develop recurrence after surgery. In recent years, immunotherapy for HCC has received growing interest, and one of the most promising strategies is the association of two immune checkpoint inhibitors (ICIs), which has already demonstrated its potential in other solid tumors such as melanoma and renal cell carcinoma. Herein, we discuss the role and the biologic rationale of dual immune checkpoint blockade in HCC patients, focusing on the two ICI combinations: nivolumab plus ipilimumab and durvalumab plus tremelimumab.
Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Ensayos Clínicos como Asunto , Humanos , InmunoterapiaRESUMEN
BACKGROUND: Biliary tract cancers (BTCs) represent a heterogeneous group of aggressive solid tumors with limited therapeutic options, and include gallbladder cancer (GBC), ampulla of Vater cancer (AVC), intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA). METHODS & RESULTS: In the current review, we will discuss recent results of clinical trials testing targeted therapies in BRAF-mutant BTCs, with a particular focus on the recently published Phase II ROAR trial and ongoing active and recruiting clinical trials. CONCLUSIONS: Although the extended use of molecular profiling has paved the way toward a new era in BTC management, targeted therapies are limited to iCCA so far, and the prognosis of patients with metastatic disease has substantially not changed in the last decade. In this discouraging scenario, BRAF inhibition is currently emerging as a novel treatment option in patients harboring BRAF mutations.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Biliar/tratamiento farmacológico , Colangiocarcinoma/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Ampolla Hepatopancreática/patología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Conductos Biliares/patología , Neoplasias del Sistema Biliar/diagnóstico , Neoplasias del Sistema Biliar/genética , Neoplasias del Sistema Biliar/mortalidad , Colangiocarcinoma/genética , Colangiocarcinoma/mortalidad , Vesícula Biliar/patología , Humanos , Terapia Molecular Dirigida/métodos , Terapia Molecular Dirigida/tendencias , Mutación , Estadificación de Neoplasias , Estudios Observacionales como Asunto , Pronóstico , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas B-raf/genética , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Hepatocellular carcinoma (HCC) represents the most frequent type of primary liver tumor. Most HCC patients present with advanced disease at diagnosis and the recurrence rate after surgery remains high. Treatment options for advanced HCC are limited, with sorafenib representing the only systemic agent approved for treatment of advanced HCC in more than a decade. However, in recent years new molecular targeted therapies and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced HCC. In particular, combinations of ICIs with antiangiogenic drugs, or with other ICIs, represent one of the most promising strategies. Herein we provide a comprehensive overview of the main therapeutic advances in the systemic treatment of HCC, focusing on the most relevant ongoing clinical trials.