Combining VEGF and PD-1/PD-L1 inhibition in advanced hepatocellular carcinoma: clinical trials, real-world evidence, and future directions.

Introduction: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide with most of patients diagnosed at advanced stage. Thus, systemic therapy remains a cornerstone of treatment. In recent years, immunotherapy has changed therapeutic scenario, being investigated also in combination with anti-vascular endothelial growth factor (VEGF) agents.

Immunosuppressive contribution of tumour-infiltrating B cells in human intrahepatic cholangiocarcinoma and their role in chemoimmunotherapy outcome.

Background: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive biliary tract cancer with a poor prognosis and a complex tumour microenvironment (TME) that remains poorly understood.

Objective: This study aimed to investigate the phenotypic and molecular characteristics of B lymphocytes, their interactions with the TME and their prognostic implications.

Design: B-cell compartments in the tumour, peritumour, and peripheral blood of iCCA patients were analysed using multimodal single-cell technologies.

Ivosidenib for IDH1-Mutant Intrahepatic Cholangiocarcinoma: Insights From a Multicenter Real-World Study.

Background & Aims: Cholangiocarcinoma (CCA) is a rare cancer with limited therapeutic options and a poor prognosis. While first-line combination therapies have improved outcomes, second-line treatment remains challenging. Ivosidenib, an IDH1 inhibitor, has shown promise in treating IDH1 mutant CCA, but real-world data is limited.

Impact of antibiotic therapy in patients with cholangiocarcinoma treated with chemoimmunotherapy.

Background: Patients with biliary tract cancers (BTC) often require antibiotic therapy before starting systemic treatment that includes an immune checkpoint inhibitor. This study aims to evaluate the prognostic impact of antibiotic therapy administered in the 15 days prior to the start of chemoimmunotherapy in patients with BTC.

Material And Methods: The study population included patients with metastatic or locally advanced BTC from western and eastern populations treated with first-line chemoimmunotherapy.

Prognostic Factors and Survival Outcomes in Resected Biliary Tract Cancers: A Multicenter Retrospective Analysis.

: Biliary tract cancers (BTCs) are aggressive malignancies with a poor prognosis. Surgery remains the only curative option, yet recurrence rates are high, and the role of adjuvant chemotherapy remains debated. This study aims to evaluate the impact of adjuvant chemotherapy and prognostic factors on survival outcomes in resected BTCs.

Efficacy of atezolizumab plus bevacizumab for unresectable HCC: Systematic review and meta-analysis of real-world evidence.

Background & Aims: Atezolizumab plus bevacizumab (A+B) is a standard-of-care treatment in unresectable hepatocellular carcinoma (uHCC). Verification of its effectiveness outside clinical trials is an area of unmet need, especially in estimating long-term survival outcomes.

Methods: We conducted a systematic review and meta-analysis of the MEDLINE, Embase, and Cochrane libraries to evaluate therapy outcomes in patients treated with frontline A+B for uHCC outside trials.

Liver transplantation in a patient with metastatic hepatocellular carcinoma after downstaging with single-agent immunotherapy: the first case report.

Background: Immunotherapy in hepatocellular carcinoma (HCC) has changed the clinical practice for unresectable and advanced setting after the approvals of atezolizumab plus bevacizumab and durvalumab plus tremelimumab (STRIDE regimen). A growing field for its application is the use of systemic therapy to achieve disease control in patients already listed for liver transplantation (LT) (bridging therapy) and fitting those not eligible within the LT criteria (conversion therapy). However, there is still a lack of prospective data for using immune checkpoint regimens in this setting, especially regarding the treatment-free interval before LT which may be different based on the immunotherapy drug chosen.

Negative impact of corticosteroid use on outcome in patients with advanced BTCs treated with cisplatin, gemcitabine, and durvalumab: A large real-life worldwide population.

In recent years, there has been increasing interest in the possible prognostic impact of concomitant medications in patients with cancer treated with immunotherapy combinations. This real-world analysis aims to evaluate the impact of concomitant medications on survival outcomes in patients with advanced biliary tract cancer (BTCs) treated with cisplatin, gemcitabine and durvalumab (CGD) therapy. The study cohort included patients with a diagnosis of advanced BTCs who were taking concomitant medications for their comorbidities before the start of CGD.

The impact of molecular alterations in patients with advanced biliary tract cancer receiving cisplatin, gemcitabine and durvalumab: a large real-life worldwide population.

Background & Aims: Cisplatin, gemcitabine, and durvalumab (CGD) combination is a standard first-line treatment for advanced biliary tract cancer (BTC). This study aimed to assess the impact of genetic alterations on outcomes in patients with advanced BTC treated with CGD in real-world clinical practice.

Methods: Patients with unresectable, locally advanced, or metastatic BTC treated with CGD across 39 centers in 11 countries (Europe, United States, and Asia) were included in this analysis.

From barriers to solutions: an expert-based algorithm for cholangiocarcinoma and other biliary tract cancers testing in the Era of precision oncology.

Introduction: Biliary tract cancer (BTC) comprises a group of aggressive malignancies with poor prognosis and limited therapeutic options. Next-generation sequencing (NGS) has advanced BTC management by identifying targetable genomic alterations. However, routine multigene NGS testing faces clinical, logistical, and economic barriers to widespread implementation.

Etiology of Hepatocellular Carcinoma May Influence the Pattern of Progression under Atezolizumab-Bevacizumab.

Background: Preclinical models have shown that metabolic dysfunction-associated steatotic liver disease (MASLD)-related hepatocellular carcinoma (HCC) may exhibit reduced responsiveness to immunotherapy, especially for intrahepatic lesions due to liver tumor microenvironment. Radiological pattern of progression has been validated in clinical studies as a useful tool for predicting outcomes in HCC undergoing systemic treatments.

Aims: The aim of this study was to determine whether MASLD influences the pattern of progression in patients treated with atezolizumab-bevacizumab.

A Prognostic Index for Advanced Biliary Tract Cancer Treated With Cisplatin, Gemcitabine and Durvalumab: The MAGIC-D Index.

Background: Over the years, prognostic indexes have been developed to help clinicians stratify patients with biliary tract cancers (BTC) into risk groups. This study aims to identify a new prognostic index for patients with BTC treated with cisplatin, gemcitabine and durvalumab (CGD) in the first-line setting.

Patients And Methods: The study population consisted of patients with BTC from 11 Eastern and Western Countries.

The Concept of "Converse Therapeutic Hierarchy" for Patients with Hepatocellular Carcinoma.

Background: The clinical complexity of patients with hepatocellular carcinoma (HCC), the availability of multiple therapeutic options, and clinical therapeutic intents could make it challenging to identify an unequivocal limit between conversion, downstaging/downsizing, and neoadjuvant therapies and curative or palliative intent treatments and to dimension the most proper sequential therapeutic strategy for each patient.

Summary: The concept of converse therapeutic hierarchy could rationally embrace all the different sequential treatment options (e.g.

Association of candidate surrogate endpoints with overall survival in advanced biliary tract cancer.

Background & Aims: Surrogate endpoints are increasingly used in biliary tract cancer (BTC) trials. While this may expedite drug approval and decrease costs, surrogate endpoints may not always correlate with an overall survival (OS) advantage. We aimed to explore the association of progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) with OS at the trial- and patient-level.

Factors associated with reaching maintenance therapy in patients with advanced biliary tract cancer treated with durvalumab: Real-world results from a multicenter and multinational study.

Standard of care first-line systemic treatment for advanced biliary tract cancer includes chemo-immunotherapy with gemcitabine, cisplatin, and durvalumab, followed by maintenance durvalumab monotherapy. The present work aims to investigate the differences in baseline clinical and molecular characteristics between patients with early progression during chemo-immunotherapy and those who reach durvalumab maintenance therapy. The study population included patients with unresectable, locally advanced, or metastatic BTC who received treatment at 38 clinical Institutions in 12 countries from July 2021 to December 2023.

Correction to "New systemic treatment paradigms in advanced biliary tract cancer and variations in patient access across Europe" [The Lancet Regional Health - Europe, volume 50, March 2025, 101170].

[This corrects the article DOI: 10.1016/j.lanepe.

The present and the future of immunotherapy in hepatocellular carcinoma and biliary tract cancers.

Hepatobiliary malignancies encompass a spectrum of invasive carcinomas arising in the liver [hepatocellular carcinoma (HCC), bile ducts [intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (EHC)] and the gallbladder. These malignancies represent a growing global health burden, with rising incidence and mortality rates and their overall prognosis remains poor because many patients present with advanced unresectable disease at diagnosis. In recent years, significant advancements in understanding HCC immunogenicity have reshaped the therapeutic scenario of advanced HCC with the immunotherapy revolutionizing the current HCC treatment landscape and patients' prognosis.

Pharmacologic features, clinical applications, and drug safety evaluation of futibatinib in the treatment of biliary tract cancer (BTC).

Introduction: Futibatinib is a small, potent, covalent, irreversible fibroblast growth factor receptor (FGFR) 1-4 inhibitor that has been added as a new standard of care for previously treated unresectable and/or advanced FGFR2 fusion/rearrangement-positive BTC. FGFR2 fusions/rearrangements play a key role in BTC survival, proliferation, invasion, and development of distant metastasis. The inhibition of this pathway is an important target in the treatment of BTC.

Efficacy and Toxicity of Pemigatinib in Advanced Cholangiocarcinoma Harboring FGFR Fusions or Rearrangements: A Systematic Review and Meta-analysis.

Background: The efficacy and safety of pemigatinib in advanced cholangiocarcinoma (aCCA) were presented in phase I-II trials and retrospective reports, with small sample sizes and variable results.

Methods: A systematic literature search included studies investigating the efficacy/safety of pemigatinib in aCCA harboring FGFR fusions/rearrangements. Primary outcomes were objective response rate (ORR) and treatment-related adverse events (AEs).