Seit September 2022 gibt es die Gastroenterologie auch für die Ohren. Der DGVS Podcast Gastro Geplauder richtet sich an Ärzt*innen, Medizinstudent*innen und alle Interessierten, die sich über aktuelle Entwicklungen und Forschungsergebnisse in der Gastroenterologie informieren möchten.
Introduction: Cancers of the biliary tract (BTC) are aggressive malignancies with limited treatment options and an overall dismal prognosis. In recent years, two concepts, namely precision oncology and immune oncology (IO) have profoundly influenced and, in some cancers, even revolutionized tumor treatments. While positive data from randomized trials have led to the incorporation of targeted concepts for genetically select BTC patients, IO is not yet implemented in clinical practice.Areas covered: We discuss published results from completed, as well as from ongoing studies on IO in BTC, based on a literature search on Pubmed and information provided by clinicaltrials.gov in October 2020. Apart from monotherapy, we outline IO-based combination approaches and highlight pivotal studies whose results will likely influence the future development of relevant concepts in BTC.Expert opinion: Despite partially positive signals, IO thus far disappointed in unselected BTC populations and should currently not be considered as a preferred systemic treatment in patients with microsatellite stable disease outside of clinical trials. In the coming years, a better understanding of the molecular mechanisms underlying resistance to checkpoint inhibition, and the identification of positive predictive biomarkers will be important for the successful integration of IO into treatment concepts for BTC patients.
Background Lenvatinib is approved as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). The efficacy of lenvatinib in Caucasian real-world patients is insufficiently defined. The purpose of this study was to evaluate the efficacy of lenvatinib in a multi-center cohort (ELEVATOR) from Germany and Austria. Methods A retrospective data analysis of 205 patients treated with first-line systemic lenvatinib at 14 different sites was conducted. Overall survival, progression free survival, overall response rate and adverse event rates were assessed and analyzed. Results Patients receiving lenvatinib in the real-world setting reached a median overall survival of 12.8 months, which was comparable to the results reported from the REFLECT study. Median overall survival (mOS) and progression free survival (mPFS) was superior in those patients who met the inclusion criteria of the REFLECT study compared to patients who failed to meet the inclusion criteria (mOS 15.6 vs 10.2 months, HR 0.55, 95% CI 0.38-0.81, p=0.002; mPFS 8.1 vs 4.8 months HR 0.65, 95% CI 0.46-0.91, p=0.0015). For patients with an impaired liver function according to the Albumin-Bilirubin (ALBI) grade, or reduced ECOG performance status ≥2, survival was significantly shorter compared to patients with sustained liver function (ALBI grade 1) and good performance status (ECOG performance status 0), respectively (HR 1.69, 95% CI 1.07-2.66, p=0.023; HR 2.25, 95% CI 1.19-4.23, p=0.012). Additionally, macrovascular invasion (HR 1.55, 95% CI 1.02-2.37, p=0.041) and an AFP ≥200 ng/mL (HR 1.56, 95% CI 1.03-2.34, p=0.034) were confirmed as independent negative prognostic factors in our cohort of patients with advanced HCC. Conclusion Overall, our data confirm the efficacy of lenvatinib as first-line treatment and did not reveal new or unexpected side effects in a large retrospective Caucasian real-world cohort, supporting the use of lenvatinib as meaningful alternative for patients that cannot be treated with IO-based combinations in first-line HCC.
Cholangiocarcinoma (CCA) is a genetically and histologically complex disease with a highly dismal prognosis. A deeper understanding of the underlying cellular and molecular mechanisms of human CCA will increase our current knowledge of the disease and expedite the eventual development of novel therapeutic strategies for this fatal cancer. This endeavor is effectively supported by genetic mouse models, which serve as sophisticated tools to systematically investigate CCA pathobiology and treatment response. These in vivo models feature many of the genetic alterations found in humans, recapitulate multiple hallmarks of cholangiocarcinogenesis (encompassing cell transformation, preneoplastic lesions, established tumors and metastatic disease) and provide an ideal experimental setting to study the interplay between tumor cells and the surrounding stroma. This review is intended to serve as a compendium of CCA mouse models, including traditional transgenic models but also genetically flexible approaches based on either the direct introduction of DNA into liver cells or transplantation of pre-malignant cells, and is meant as a resource for CCA researchers to aid in the selection of the most appropriate in vivo model system.
Introduction: Hepatocellular carcinoma (HCC) is one of the most common and deadliest cancers worldwide. In recent years, several drugs have been approved in first- and second-line setting. Currently, several phase-III trials are ongoing with combinations of checkpoint inhibitors, tyrosine kinase inhibitors (TKI) and anti-angiogenic antibodies, which will most likely increase therapeutic options in frontline therapy in the near future.Areas covered: This review summarizes the standard of care in first-line systemic therapy for patients with advanced HCC and provides an outlook on the most promising combinations currently tested in prospective trials.Expert opinion: The recent approval of novel substances has substantially changed the field of palliative treatment strategies in patients with advanced HCC. Immuno-oncology (IO)-based combination therapies will become the next standard of care in frontline HCC. The potent anti-tumor efficacy and good tolerability of these therapies will increase the use of upfront systemic therapy in patients with intermediate stage HCC.
