Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: A large real-life worldwide population.

Background: The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a global multicenter retrospective analysis of its first-line treatment outcomes.

Methods: We included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab, gemcitabine, and cisplatin at 39 sites in 11 countries (Europe, the United States, and Asia).

Multicenter phase I/II trial of gemcitabine, oxaliplatin and nab-paclitaxel as first-line treatment for patients with advanced biliary tract cancer.

Introduction: The prognosis of patients with advanced biliary tract cancer (BTC) is still poor, and new strategies improving patients' outcome are needed. In our trial we investigated safety and activity of nab-paclitaxel in combination with gemcitabine and oxaliplatin as first-line systemic treatment for patients with advanced BTC.

Methods: In this investigator-initiated, multicenter, dose-escalation, single-arm phase I/II trial, patients were accrued into cohorts of 3 patients and dose escalation was performed following the standard 3 + 3 rule.

Durvalumab Plus Gemcitabine and Cisplatin Versus Gemcitabine and Cisplatin in Biliary Tract Cancer: a Real-World Retrospective, Multicenter Study.

Background: The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed cell death ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC).

Objective: The present study investigated for the first time the impact on survival of adding durvalumab to cisplatin/gemcitabine compared with cisplatin/gemcitabine in a real-world setting.

Patients And Methods: The analyzed population included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab in combination with cisplatin/gemcitabine or with cisplatin/gemcitabine alone.

Different Genomic Clusters Impact on Responses in Advanced Biliary Tract Cancer Treated with Cisplatin Plus Gemcitabine Plus Durvalumab.

Background: The results reported in the TOPAZ-1 phase III trial led to the approval of the combination of cisplatin and gemcitabine with durvalumab as the new first-line standard of care for patients with locally advanced or metastatic cholangiocarcinoma.

Objective: We performed a clustering analysis to classify patients into different groups based on their mutation profile, correlating the results of the analysis with clinical outcomes.

Methods: We selected 51 patients with cholangiocarcinoma who were treated with the combination of chemotherapy and durvalumab and who were screened using the next-generation sequencing-based FoundationOne gene panel.

Comparative Genomic Analysis and Clinical Outcomes of BRAF-mutated Advanced Biliary Tract Cancers.

Purpose: BRAF mutations are rare in biliary tract cancers (BTC), but are of interest given the recent developments in targeted therapy for BTC. We investigated the clinical outcomes in a cohort of BRAF-mutant advanced BTC treated with first-line chemotherapy. Furthermore, we investigated the genomic landscape of BRAF class I, II, and III mutations in the intrahepatic cholangiocarcinoma (iCCA) subgroup of BTC.

Updated survival outcomes with ivosidenib in patients with previously treated IDH1-mutated intrahepatic-cholangiocarcinoma: an Italian real-world experience.

Background: The results of the phase III ClarIDHy trial led to the FDA approval of ivosidenib as a therapeutic option for patients with locally advanced or metastatic cholangiocarcinoma (CCA) harboring isocitrate dehydrogenase 1 (IDH1) mutations. We recently published the first data on the use of ivosidenib in a real-world setting.

Objective: Here we report the updated survival results of 11 patients with locally advanced or metastatic IDH1-mutated CCA who received ivosidenib in clinical practice.

Clinical Outcomes After Progression on First-Line Therapies in IDH1 Mutated Versus Wild-Type Intrahepatic Cholangiocarcinoma Patients.

Background: Isocitrate dehydrogenase-1 (IDH1) mutations occur in a significant proportion of intrahepatic cholangiocarcinomas (iCCAs). No data are available regarding the prognostic impact of IDH1 mutations in advanced iCCA patients after progression on first-line therapies.

Objective: We investigated the role of IDH1 mutation in advanced iCCA after progression on first-line therapies.

The oncological multidimensional prognostic index is a promising decision-making tool: A real-world analysis in older patients with metastatic colorectal cancer.

Background: Approximately 50% of colorectal cancers occur in older patients. International societies recommend geriatric tools to optimise treatment of older patients. Comprehensive Geriatric Assessment (CGA) is a multidimensional assessment used to classify patients as fit, vulnerable, or frail.

Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma.

IDH1-mutated cholangiocarcinomas (CCAs) are an interesting group of neoplasia with particular behavior and therapeutic implications. The aim of the present work is to highlight the differences characterizing IDH1m and IDH1wt CCAs in terms of genomic landscape. 284 patients with iCCA treated for resectable, locally advanced or metastatic disease were selected and studied with the FOUNDATION Cdx technology.

Determinants of Treatment Benefit and Post-Treatment Survival for Patients with Hepatocellular Carcinoma Enrolled in Second-Line Trials after the Failure of Sorafenib Treatment.

Second-line treatments are standard care for advanced hepatocellular carcinoma (HCC) patients with preserved liver function who are intolerant of or progress on first-line therapy. However, determinants of treatment benefit and post-treatment survival (PTS) remain unknown. HCC patients previously treated with sorafenib and enrolled in second-line clinical trials were pooled according to the investigational treatment received and the subsequent regulatory approval: approved targeted agents and immune checkpoint inhibitors (AT) or other agents (OT) not subsequently approved.

Next-generation sequencing analysis of cholangiocarcinoma identifies distinct IDH1-mutated clusters.

Background: IDH1-mutated intrahepatic cholangiocarcinomas (IDH1m iCCAs) could be treated with anti-IDH1 drugs, although the high heterogeneity in this class of tumours could limit treatment efficacy.

Methods: We selected 125 IDH1m iCCAs that were treated as resectable, locally advanced, or metastatic and were screened by the NGS-based FoundationOne gene panel. We conducted a mutation-based clustering of tumours and survival analysis.

Platinum sensitivity in patients with IDH1/2 mutated vs wild-type intrahepatic cholangiocarcinoma: A propensity score-based study.

Isocitrate dehydrogenase (IDH)1/2 mutations are the most frequent druggable alterations in intrahepatic cholangiocarcinoma (iCCA), reported in ~20% of cases. Preclinical evidence indicates that these mutations are associated with homologous recombination deficiency (HRD), which could be exploited as a target for platinum chemotherapy (ChT) and PARP inhibitors. However, the role of IDH1/2 mutations as surrogate biomarkers for platinum efficacy is unknown.

Simultaneous Care in Oncology: A 7-Year Experience at ESMO Designated Centre at Veneto Institute of Oncology, Italy.

Benefits of early palliative care referral in oncology are well-validated. At the Veneto Institute of Oncology-IRCCS, a simultaneous-care outpatient clinic (SCOC) has been active since 2014, where patients with advanced cancer are evaluated by an oncologist together with a palliative care team. We prospectively assessed SCOC patients’ characteristics and SCOC outcomes through internal procedure indicators.

Prognostic impact of FGFR2/3 alterations in patients with biliary tract cancers receiving systemic chemotherapy: the BITCOIN study.

Aim: FGFR2 rearrangements have been identified as a novel therapeutic target of biliary tract cancer (BTC). However, reliable prevalence estimates of this molecular alteration and its prognostic role have not been fully elucidated.

Methods: A retrospective mono-institutional series of 286 patients affected by locally advanced or metastatic BTC (183 intrahepatic cholangiocarcinomas, 67 extrahepatic cholangiocarcinomas, 36 gallbladder carcinomas) was profiled by means of targeted DNA/RNA next-generation sequencing, immunohistochemistry and fluorescence in situ hybridisation for FGFR2/3, ERBB2, NTRK alterations, IDH1/2 and BRAF mutations and DNA mismatch repair complex proteins alterations/microsatellite instability.

Advances in pharmacotherapy for cholangiocarcinoma: from conventional therapies to targeted drugs.

Introduction: Cholangiocarcinomas (CCA) are rare, highly invasive tumors often diagnosed at an advanced disease stage with an associated poor prognosis. Surgery represents the only chance for curative-intent treatment, but recurrence rates remain high. Neoadjuvant or adjuvant chemotherapy are options for patients with resectable CCA to increase recurrence-free survival and overall survival, while palliative chemotherapy represents the treatment for unresectable disease.

Identification of Regorafenib Prognostic Index (REP Index) via Recursive Partitioning Analysis in Patients with Advanced Hepatocellular Carcinoma Receiving Systemic Treatment: A Real-World Multi-Institutional Experience.

Background: The results of the pivotal RESORCE trial led to the approval of the tyrosine kinase inhibitor regorafenib as second-line treatment in advanced hepatocellular carcinoma (HCC) after sorafenib failure. Data about prognostic factors in a second-line HCC setting are scarce.

Objective: The aim of the present study was to investigate prognostic factors in a cohort of patients with advanced HCC treated with regorafenib after progressing on sorafenib.

Real-Life Clinical Data of Cabozantinib for Unresectable Hepatocellular Carcinoma.

Introduction: Cabozantinib has been approved by the European Medicine Agency (EMA) for hepatocellular carcinoma (HCC) previously treated with sorafenib. Cabozantinib is also being tested in combination with immune checkpoint inhibitors in the frontline setting. Real-life clinical data of cabozantinib for HCC are still lacking.

Detection of Molecular Residual Disease Using Personalized Circulating Tumor DNA Assay in Patients With Colorectal Cancer Undergoing Resection of Metastases.

Purpose: More than 50% of patients with stage IV colorectal cancer (metastatic colorectal cancer [mCRC]) relapse postresection. The efficacy of postoperative systemic treatment is limited in this setting. Thus, these patients would greatly benefit from the use of a reliable prognostic biomarker, such as circulating tumor DNA (ctDNA) to identify minimal or molecular residual disease (MRD).

Role of the prognostic nutritional index in predicting survival in advanced hepatocellular carcinoma treated with regorafenib.

Aim: A link has been established between malnutrition, immunological status, and hepatocellular carcinoma (HCC). The prognostic nutritional index (PNI) has been recognized as a prognostic indicator in early-stage HCC and in patients treated with first-line therapy. However, to date, the role of the PNI in HCC patients treated with regorafenib has not been reported.

Regorafenib versus cabozantinb as second-line treatment after sorafenib for unresectable hepatocellular carcinoma: matching-adjusted indirect comparison analysis.

Background: Recently, three published phase III trials highlighted the superiority of investigational drugs compared to placebo, thus leading to their approval in the second-line setting. We report here a MAIC of second-line MKI options for patients with HCC previously treated with sorafenib using individual real-world data of regorafenib and aggregate data of second-line cabozantinib from the CELESTIAL trial.

Methods: Data from 278 patients who received regorafenib as second-line therapy after sorafenib failure for unresectable HCC were used as IPD.