INTRODUCTION:Biliary tract cancers (BTCs) are molecularly heterogeneous, and early genomic profiling is becoming increasingly important for treatment decisions. Because tissue sampling is often limited or inadequate, there is a clear need for minimally invasive biomarkers that can support treatment selection and longitudinal disease assessment. AREAS COVERED:This narrative review summarizes current and emerging liquid-biopsy (LB) applications in BTC, with a primary focus on plasma circulating tumor DNA (ctDNA). The evidence base was assembled through targeted searches of PubMed/MEDLINE and Embase up to 1 February 2026, supported by selective ClinicalTrials.gov searches for ongoing biomarker-driven studies. We discuss ctDNA-based molecular profiling for actionable alterations, its prognostic role including minimal residual disease assessment, and its use in serial monitoring of treatment response and acquired resistance. We also consider how LB may support clinical-trial enrichment and biomarker-guided endpoints, and briefly review complementary approaches using bile and other analytes, while highlighting current evidence gaps. EXPERT OPINION:In BTC, ctDNA is best viewed as a complement to tissue-based profiling, especially when tissue is inadequate or when rapid genotyping is needed. Its broader clinical impact will depend on assay standardization, clearer interpretation frameworks for low-shedding disease, and prospective studies showing that ctDNA-guided decisions improve patient outcomes.

PURPOSE:Gastrointestinal stromal tumors (GIST) are molecularly heterogeneous neoplasms defined by mutually exclusive driver alterations (KIT, PDGFRA, SDH, BRAF, RAS and NF1). However, driver mutations alone do not fully explain their biological and clinical variability. Chromosomal imbalances and loss of heterozygosity (LOH) may represent an additional layer of tumor characterization. We developed a single-nucleotide polymorphism (SNP)-based next-generation sequencing (NGS) panel enabling genome-wide LOH assessment from formalin-fixed paraffin-embedded tissue. MATERIALS AND METHODS:Forty-nine GIST cases molecularly classified by targeted NGS (KIT n=19, PDGFRA n=9, SDH-deficient n=8, NF1 n=7, quadruple wild type [qWT] n=6) were analyzed. LOH was inferred from variant allele frequency patterns across 1,826 genome-wide SNPs. RESULTS:Chromosome 14 was the most commonly affected (63%), followed by chromosomes 22 (45%), 15 (41%), 21 (27%), and 13 (20%). Loss of chromosome arm 1p occurred in 43% of tumors. Distinct subgroup-specific patterns emerged: KIT-mutant GIST exhibited the highest degree of genomic instability, whereas both SDH-deficient tumors and PDGFRA-mutant GIST displayed minimal chromosomal instability. NF1-mutant tumors showed recurrent single-arm chromosome 17 LOH. qWT GISTs were heterogeneous, including one case with extensive chromosomal instability. CONCLUSIONS:Genome-wide SNP-based LOH profiling reveals distinct, subgroup-specific patterns of chromosomal imbalance in GIST and may serve as a feasible complementary approach to driver mutation analysis for refined molecular characterization and potential future clinical utility.

Background: Advanced biliary cancer (ABC) is still regarded as an incurable condition. However, the improved depth and duration of response enabled by chemo-immunotherapy may foster intensified strategies, including surgical procedures, radiotherapy and intra-arterial techniques. Objectives: The prevalence, clinical features and treatment outcomes of ABC receiving multimodality treatment in the immunotherapy era are unknown. Design: Newly diagnosed ABC treated with chemo-immunotherapy and loco-regional procedures from February 2022 to December 2024 were retrospectively identified at 10 tertiary referral cancer centres in Italy. Methods: Categorical variables were compared using the chi-squared test, and the inverse probability of treatment weighting analysis was performed to reduce selection biases. Results: Of 241 ABC receiving first-line treatment, 12 (4.9%) fulfilled the inclusion criteria. The median age was 69 (range 36–80), and 9 patients (75%) had intrahepatic cholangiocarcinoma (iCCA). Ten (83.3%) presented with de novo unresectable ABC: 3 (25%) had locally advanced, and 7 (50.3%) had metastatic disease. The median number of metastatic sites was one, with lymph nodes being the most commonly involved location (41.6%, n = 5). Patients treated with intensified therapy were more likely to have low tumour burden ( p = 0.03) and iCCA ( p = 0.06). Overall, four patients underwent surgery, three transarterial radioembolization, three stereotactic body radiotherapy and two liver transplants. As of data cut-off, 11 patients were alive (91.6%), and five patients were disease-free (41.6%). After adjusting for age, gender, Eastern Cooperative Group Performance Status (ECOG PS), primary site, disease status and number of metastases, the overall survival for the multimodality strategy versus systemic treatment alone was not reached versus 14.1 months ( p < 0.001). Conclusion: This study, the first on multimodality treatment of ABC in the immunotherapy era, suggests that a highly selected subset of patients may achieve long-term disease control with an intensified approach. Oligometastatic patients and those affected by iCCA appear as the best candidates. Future studies are needed to confirm these preliminary findings.

The results of a recent trial undoubtedly contribute a vital element to the overarching management of rare tumors and offer new treatment hopes for patients with brain metastases, thereby paving the way for future research in immunotherapy. See related article by Ahluwalia et al., p. 1928.

INTRODUCTION:Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, largely arising in the setting of chronic liver disease and cirrhosis. Given the immunosuppressive hepatic tumor microenvironment, optimizing immunotherapeutic strategies is critical to improve patient outcomes. AREAS COVERED:This review examines the biological rationale and clinical evidence supporting dual immune checkpoint inhibition with nivolumab plus ipilimumab in advanced HCC. We discuss mechanisms of immune tolerance in cirrhosis and tumor progression, including regulatory T cells, myeloid-derived suppressor cells, hypoxia, metabolic reprogramming, and T-cell exhaustion. Key clinical data from early-phase studies, such as CheckMate 040 and the phase III CheckMate 9DW, are analyzed, focusing on overall survival, response rates, and durability of response compared with tyrosine kinase inhibitors. A structured literature search of PubMed, Embase, and major oncology congress proceedings was conducted to identify relevant preclinical and clinical studies. EXPERT OPINION:Dual checkpoint blockade represents an effective first-line option for selected patients with advanced HCC, offering meaningful survival benefit at the cost of increased immune-related toxicity. Future progress depends on improved patient selection, biomarker development, and rational combination strategies.

Computational pathology enables the automatic tissue analysis of Whole Slide Images (WSIs), offering unmatched possibilities to capture quantitative tumor microenvironment (TME) characteristics that are essential for patients' prognosis and therapy response. The existing clinical and digital biomarkers do not encompass the morphometric features and spatial interactions between vascular networks and immunological compartment in the TME. To address this challenge, this work presents a high- throughput quantitative framework for automatic segmentation and assessment of aberrant phenotypes of blood vessels and immune cell clusters in hematoxylin & eosin-stained WSIs, to construct the Vascular-Immune Pathomic (VIPath) biomarker. For our study, we utilized three public datasets of Colon Adenocarcinoma (COAD) and Stomach Adenocarcinoma (STAD) from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) projects: TCGA-COAD, TCGA-STAD, and CPTAC-COAD. Additionally, we collected two in-house gastric cancer cohorts of 80 and 51 patients : DBGC-M0 and DBGC-M1. The VIPath biomarker was incorporated in a Cox proportional hazards model trained on the TCGA-COAD. Then, it was validated for predicting Overall Survival (OS) in TCGA-STAD, DBGC-M0, and DBGC-M1, Disease Free Survival in CPTAC-COAD and second-line therapy Progression-free Survival (PFS-2) in DBGC-M1. VIPath encompasses features from both vascular and immunological compartments interacting in the TME. Results proved that VIPath was capable to significantly stratify risk groups for OS TCGA-STAD (p=0.018), OS DBGC-M0 (p=0.029), OS DBGC-M1 (p=0.014), and PFS-2 DBGC-M1 (p$< $0.005). Furthermore, when inserted in a Cox model, it led to an improvement of C-index and R2 over all other considered prognostic factors, i.e., p-TNM, ECOG, MSI, HER2.

BACKGROUND AND OBJECTIVE:Combining targeted therapeutics can significantly help address the dynamic changes in cancer biology abnormalities and thus improve the duration of response and outcome. However, the efficacy of such approaches is highly dependent on the combination, interactions, and timing between the administered drugs. Current clinical trials can test only a low number of schedules with fixed designs. Pharmacometric tools can assist in exploring and selecting the most effective drug dosages and schedules by modeling traits of patients with different clinical and biological characteristics. METHODS:This study proposes a pharmacokinetic-pharmacodynamic model describing the networked system of tumor development and angiogenesis under the control of antiangiogenic and cytotoxic, i.e., Ramucirumab and Paclitaxel second-line combination therapy. A two-step scalable algorithm is proposed to calibrate model parameters and match virtual to real population therapy outcomes, followed by fine-tuning directly on the Progression-free Survival (PFS)-2 Kaplan-Meier curve. Two cohorts of advanced gastric cancer patients were considered: a calibration cohort from South Korea, and an external verification cohort from IRCCS "S. De Bellis", an Italian research hospital. These real-world patients had heterogeneous clinical starting conditions. We perform prospective evaluations of new combination regimens that adhere to pharmacological constraints that are paramount for clinical translation, in which the administration time of the cytotoxic agent is triggered by the normalization window opening, monitored by a tumor microenvironment digital biomarker. RESULTS:The calibration procedure led to the discovery of a new mathematical biomarker describing the influence of intrinsic tumor growth and angiogenesis on treatment outcomes. The predictive value was assessed through the log-rank test between two PFS-2 groups, which exhibited different (p-value <0.0001) therapy response trends. Our results showcase a new regimen that, by using 33% less cytotoxic drug, achieves indistinguishable PFS-2. Additionally, we present another regimen that extends PFS-2 from 49.2% to 60.9% after 121 days of therapy (p-value <0.0001), by using the same dosing as the standard protocol. CONCLUSIONS:This study proposes an in-silico quantitative platform for virtual expansion of real-world patient cohorts. Furthermore, the estimation of the efficacy of adaptive dose schedules of a combined therapy can complement and inform clinical trial design.

Background and aimsLiquid biopsy offers a minimally invasive tool to detect actionable mutations, monitor minimal residual disease (MRD), and guide therapy in gastrointestinal (GI) cancers. We critically review the clinical utility of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and small extracellular vesicles (sEVs) across GI malignancies and propose a framework for their integration into clinical practice.MethodsWe synthesized evidence from over 200 studies, including prospective trials and translational research, to assess diagnostic accuracy, prognostic value, and clinical actionability of each biomarker type in esophageal, gastric, colorectal, pancreatic, hepatocellular, and biliary cancers.ResultsctDNA has shown strong potential for MRD detection and treatment monitoring, particularly in colorectal and pancreatic cancer. CTCs offer insights into metastatic risk and therapeutic resistance, while sEVs provide molecular cargo relevant to immunomodulation and disease progression. Emerging microfluidics and AI-driven multi-omics approaches may overcome current limitations.ConclusionThe integration of liquid biopsy technologies into GI oncology holds promise for early detection and precision therapy. We propose a five-phase clinical roadmap and outine the key research gaps that need to be addressed before widespread implementation in routine care.

Background: Gastric cancer (GC) is a highly aggressive disease often complicated by resistance to chemotherapy agents like paclitaxel (PTX), which targets microtubules to induce apoptosis. Resistance arises through complex molecular mechanisms, including the overexpression of pro-angiogenic factors (VEGFA, ANG-2), activation of survival pathways (PDGFRβ, PPARγ), and epithelial-mesenchymal transition (EMT) driven by proteins such as VIM, E-CAD, N-CAD, and FLOT-1. The extracellular matrix (ECM), regulated by COL1A1 and influenced by PPARγ, acts as a physical barrier to drug penetration. Small extracellular vesicles (sEVs) have emerged as critical mediators of intercellular communication and may influence these resistance pathways. Methods: This study investigated the role of sEVs isolated from metastatic GC patients treated with Ramucirumab and PTX. Patients were stratified by progression-free survival (PFS) into rapidly progressing (RP) and controlled disease (CD) groups. sEVs from these patients were applied to HCEC-1CT and HEPA-RG cell lines. Cell viability assays, gene and protein expression analyses, and bioinformatic studies were conducted to assess the impact of sEVs on resistance-related markers. Results: Results showed that sEVs from CD patients reduced the expression of markers associated with drug resistance, while sEVs from RP patients increased these markers, promoting angiogenesis, EMT, and ECM remodeling. These changes correlated with enhanced cell survival and resistance phenotypes. Bioinformatic analyses confirmed that sEVs modulate inflammation, ECM dynamics, and EMT pathways. Conclusions: In conclusion, sEVs from metastatic GC patients significantly influence chemoresistance and tumor progression. Targeting sEV-mediated signaling may offer novel therapeutic strategies to overcome resistance and improve treatment outcomes in gastric cancer.

Molecular analysis is mandatory in the diagnostic work-up of gastrointestinal stromal tumors (GISTs). Indeed, it is essential for clinical decisions, from patients’ selection for systemic treatment to identifying unrecognized syndromic conditions. Since GISTs are recognized as a heterogeneous family of different clinical entities, molecular analysis should also require a feasible, rapid, and reliable diagnostic workflow. Herein, we present our experience on the performance and clinical utility of two lab-developed multigene-NGS panels specifically built for GIST analysis. Among 163 analyzed GISTs, 72.4% carried KIT mutations while 11.0% were PDGFRA-mutant. Among putative KIT/PDGFRA WT cases that arrived at our attention from an external analysis, nine of 10 were found carrying either KIT or PDGFRA pathogenic mutations by our panel. On 26 KIT/PDGFRA/BRAF WT patients at the first level, the second level panel identified NF1 or SDHA mutations in 16 cases, while 10 patients did not display any mutation, except for two of them found as carriers of SDHC epimutation. This optimized NGS diagnostic approach helps to characterize the molecular profiles of GIST and drastically reduces the number of truly non-KIT and non-PDGFRA-addicted GIST cases.

Background & Aims:Durvalumab plus tremelimumab (STRIDE) has emerged as a first-line systemic treatment option for unresectable hepatocellular carcinoma (HCC). This international multicentre study aimed to evaluate the efficacy and tolerability of STRIDE or durvalumab monotherapy in routine clinical practice, comparing outcomes between patients within and outside key eligibility criteria for the HIMALAYA trial. Methods:From a database of 1,423 patients with advanced/unresectable HCC treated with immunotherapy across 35 centres, we analysed 233 patients receiving STRIDE or durvalumab monotherapy. Patients were categorized as HIMALAYA-IN or HIMALAYA-OUT based on key trial eligibility criteria (no prior systemic therapy, ECOG-PS 0-1, Child-Pugh class A, no Vp4 thrombosis). Baseline characteristics were assessed for overall survival (OS) and hepatic decompensation using a multivariable Cox model and competing-risk analysis, respectively. Objective response rates and treatment-related adverse events were recorded. Results:Of the 233 patients, 123 (53%) were HIMALAYA-IN and 110 (47%) were HIMALAYA-OUT. STRIDE was given in 95% of HIMALAYA-IN patients. After median follow-up of 6.0 months, median OS was 20.4 months (95% CI 11.7-NR) in the overall population. HIMALAYA-IN patients achieved significantly longer OS than HIMALAYA-OUT patients (23.0 vs. 12.2 months; hazard ratio 0.61; 95% CI 0.39-0.96; p = 0.03). Macrovascular invasion and hepatic decompensation were independent negative prognostic factors in the whole cohort. Hepatic decompensation occurred in 10.5% of patients within 12 months from treatment start. Objective response rate was 23.7% and 17.8% of HIMALAYA-IN and -OUT patients, respectively. Patients achieving disease control (whole cohort: 59.4%) demonstrated 24-month OS of 58.2% in HIMALAYA-IN and 44.8% in HIMALAYA-OUT groups. Grade 3-4 treatment-related adverse events occurred in 16.3% of patients. Conclusions:STRIDE shows reproducible effectiveness and an acceptable safety profile in real-world practice. Achieving disease control and maintaining liver function emerged as key determinants of long-term survival benefit. Impact and implications:The DT-real study validates the efficacy and safety of STRIDE (durvalumab plus tremelimumab) in routine clinical practice, with HIMALAYA trial-eligible patients achieving 23-month median survival, and showing a safety profile comparable to that observed in the pivotal trial. Nearly half of real-world patients received treatment despite not meeting original trial criteria, reflecting urgent clinical need in this population with limited therapeutic options. As for other immunotherapy-based combinations, hepatic decompensation is a critical determinant of survival. Patients achieving disease control demonstrated substantially improved 24-month overall survival rates compared to those with progressive disease, confirming the findings of the exploratory analyses of the HIMALAYA trial.

Background/Objectives: Biliary tract cancers (BTCs) are aggressive neoplasms with limited therapeutic options. The amount of prospective evidence is poor, and limited data are available on the impact of treatment sequencing on survival. Here we report a real-world experience of patients with advanced BTC treated with at least three lines of therapy. We evaluated the impact of sequential treatments, and we further compared the efficacy of Gemcitabine/Cisplatin (GemCis) and mFOLFOX to other first- and second-line chemotherapy regimens, respectively. Methods: Data on 60 patients with locally advanced or metastatic BTC under the care of a single Italian referral hospital and treated with at least three lines of chemotherapy were retrospectively collected. Data from 56 patients were included in the analysis. Survival analyses were performed using R software (v1.2.5042). Results: We compared the outcomes of patients treated according to the “standard” pre-immunotherapy sequence (GemCis and mFOLFOX in the first and second lines, respectively) versus those treated with all other combinations (“control” group). Our analysis did not show significant survival differences between the two groups. However, it should be noted that we selected long-survival patients by including only those who received at least three or more lines of chemotherapy. Focusing on the first-line setting, no significant differences in both mPFS and mOS emerged by comparing GemCis versus other doublets (mainly Gemcitabine/Oxaliplatin). Similarly, mPFS and mOS from second-line treatment did not statistically differ between patients treated with mFOLFOX versus those treated with other regimens (71% chemotherapy doublets). Conclusions: Our series provides real-world outcomes of patients with advanced BTC before the approval of immunotherapy. Even considering the monocentric and retrospective design, our study represents one of the first analyses on the impact of sequential treatment strategies in patients with BTC.

Treatment options for intrahepatic cholangiocarcinoma (iCCA), a highly malignant tumor with poor prognosis, are limited. Recent developments in immunotherapy and immune checkpoint inhibitors (ICIs) have offered new hope for treating iCCA. However, several issues remain, including the identification of reliable biomarkers of response to ICIs and immune-based combinations. Tumor immune microenvironment (TIME) of these hepatobiliary tumors has been evaluated and is under assessment in this setting in order to boost the efficacy of ICIs and to convert these immunologically “cold” tumors to “hot” tumors. Herein, the review TIME of ICCA and its critical function in immunotherapy. Moreover, this paper also discusses potential avenues for future research, including novel targets for immunotherapy and emerging treatment plans aimed to increase the effectiveness of immunotherapy and survival rates for iCCA patients.

Angiogenesis inhibition treatments are limited and are often too late for advanced gastric cancer (GC) patients, in whom its efficacy is reduced. New molecular biomarkers are needed to optimize therapy regimens. In regard to this framework, circulating miRNAs, with high sensitivity and specificity, could be useful biomarkers of GC. The present longitudinal study was focused on analyzing the expression levels of a blood miRNA signature in a cohort of 40 patients receiving second-line therapy combining Ramucirumab and Paclitaxel, stratified based on their Progression-Free Survival (PFS). Using differential and bioinformatic analysis, miR-205-5p, miR-30e-3p, and miR-23b-3p were selected as possible predictive biomarkers, with the results showing that they were more highly expressed in patients exhibiting longer PFS and that they were involved in modulating angiogenesis. Furthermore, patients with longer PFS showed a progressive and significant decrease in the selected miRNA to minimal levels. The loss of the protective effect and the increased expression of the hypothetical targets, including angiopoietin-2, were then observed. The hypothesis was supported by the inverse correlation found for miR-205-5p and angiopoietin-2. Circulating levels of miR-205-5p were protective (HR = 0.37, p = 0.02) and patients with higher baseline miRNA levels had longer OS (12.47 vs. 9.00 months). Our findings suggest that these three miRNAs may be novel candidates as non-invasive predictive markers of therapy outcomes.

INTRODUCTION:Recently, immunotherapy has offered new hope for treating biliary tract cancer (BTC). However, several issues are to be considered, including the lack of validated predictive biomarkers that could help to identify patient groups which are most likely to benefit from such therapeutic approaches. AREAS COVERED:In the current article, we will provide an overview of recent results and ongoing and future research directions of immunotherapy in BTC, with a special focus on recently published, practice-changing data, and ongoing active and recruiting clinical trials. EXPERT OPINION:At this moment, dozens of clinical trials in phases I to III are evaluating the role of cancer immunotherapy in this setting, with the hope of adding more therapeutic options for BTC patients. Future research must focus on the development of novel agents and combinations, but the validation of biomarkers remains an urgent need. As more research results emerge, novel combinatorial strategies are destined to further transform the treatment paradigm for this heterogeneous and aggressive tumor type.

Autotaxin (ATX) is a member of the ectonucleotide pyrophosphate/phosphodiesterase (ENPP) family; it is encoded by the ENPP2 gene. ATX is a secreted glycoprotein and catalyzes the hydrolysis of lysophosphatidylcholine to lysophosphatidic acid (LPA). LPA is responsible for the transduction of various signal pathways through the interaction with at least six G protein-coupled receptors, LPA Receptors 1 to 6 (LPAR1–6). The ATX–LPA axis is involved in various physiological and pathological processes, such as angiogenesis, embryonic development, inflammation, fibrosis, and obesity. However, significant research also reported its connection to carcinogenesis, immune escape, metastasis, tumor microenvironment, cancer stem cells, and therapeutic resistance. Moreover, several studies suggested ATX and LPA as relevant biomarkers and/or therapeutic targets. In this review of the literature, we aimed to deepen knowledge about the role of the ATX–LPA axis as a promoter of cancer development, progression and invasion, and therapeutic resistance. Finally, we explored its potential application as a prognostic/predictive biomarker and therapeutic target for tumor treatment.

In The Lancet Gastroenterology & Hepatology, Do-Youn Oh and colleagues 1 Oh D-Y He AR Bouattour M et al. Durvalumab or placebo plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study. Lancet Gastroenterol Hepatol. 2024; (published online May 29. https://doi.org/10.1016/S2468-1253(24)00095-5.) Google Scholar report the updated analysis of the pivotal TOPAZ-1 study, a phase 3, global, randomised trial assessing the role of the anti-PD-L1 durvalumab plus chemotherapy as first-line treatment compared with chemotherapy alone in patients with biliary tract cancer. The experimental group showed a statistically significant benefit in overall survival at the preplanned interim analysis of TOPAZ-1, which was published in 2022, with a hazard ratio (HR) of 0·80 (95% CI 0·66–0·97; p=0·021) and an estimated 24-month overall survival rate of 24·9% (95% CI 17·9–32·5) for durvalumab and 10·4% (4·7–18·8) for placebo. 2 Oh D-Y Ruth He A Qin S et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022; 1 (EVIDoa2200015) Crossref PubMed Google Scholar Furthermore, the addition of durvalumab to gemcitabine–cisplatin improved progression-free survival (7·2 months vs 5·7 months) and overall response rate (26·7% vs 18·7%) compared with placebo plus gemcitabine–cisplatin. Considering these results, the US Food and Drug Administration and European Medical Agency approved durvalumab in combination with chemotherapy for patients with advanced biliary tract cancer as the new gold-standard first-line treatment. 3 Kelley RK Ueno M Yoo C et al. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023; 401: 1853-1865 Summary Full Text Full Text PDF PubMed Scopus (150) Google Scholar , 4 Burris III, HA Okusaka T Vogel A et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2024; 25: 625-635 Summary Full Text Full Text PDF Scopus (0) Google Scholar Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 studyDurvalumab plus gemcitabine–cisplatin showed robust and sustained overall survival benefit with no new safety signals. Findings continue to support the regimen as a standard of care for people with untreated, advanced biliary tract cancer. Full-Text PDF

Studies conducted in the last few years have suggested a connection between clinical outcomes and the time of immune checkpoint inhibitors (ICIs) infusion. However, few data are available regarding the differences between early and late time-of-day (ToD) administration in metastatic renal cell carcinoma (mRCC) patients receiving immunotherapy and immune-based combinations. In this meta-analysis, we aimed to fully investigate the influence of timing of administration on the efficacy of mRCC immunotherapy, by comparing early ToD versus late ToD dosing in this setting. The present systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Overall Survival (OS) was measured as Hazard Ratios (HRs) and 95

ABSTRACT Background Despite all the improvements achieved over the last decade, the use of immune checkpoint inhibitors (ICIs) has been associated to a wide range of adverse drug events, which are frequently markedly different from those observed with cytotoxic chemotherapy and targeted therapies, such as sorafenib. Research design and methods We performed a meta-analysis with the aim to compare grade 3/4 treatment-related adverse events (TRAEs), grade 5 TRAEs, serious TRAEs, and TRAEs leading to discontinuation in ICIs versus sorafenib across phase III clinical trials of first-line treatment for advanced hepatocellular carcinoma (HCC). Results Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Patients treated with ICIs showed higher risk of serious TRAEs (OR 1.48, 95% CI = 1.16–1.9) while sorafenib treatment was associated with higher risk of TRAEs leading to discontinuation (OR 0.65, 95% CI = 0.48–0.89). No differences in grade 3/4 TRAEs and grade 5 TRAEs. Conclusions Beyond activity and efficacy, careful consideration should be given to toxicity while choosing the appropriate first-line treatment in HCC.