bevacizumab (Stivant / BE 1040V / BE1040V)

Study protocol of a prospective, non-interventional cohort study evaluating the benefits of transjugular intrahepatic portosystemic shunt in patients with hepatocellular carcinoma receiving first-line atezolizumab plus bevacizumab (NISTIPS TRITICC-4, IKF092).

Angendohr Carolin C, Weigel Christian C, Kunstein Anselm A, Joerdens Markus M et al.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with most patients diagnosed at an advanced stage. Atezolizumab plus bevacizumab is a current standard first-line therapy; however, outcomes are strongly influenced by underlying cirrhosis and clinically significant portal hypertension (CSPH). Complications such as ascites and variceal bleeding may limit treatment continuation, particularly as bevacizumab increases bleeding risk. Transjugular intrahepatic portosystemic shunt (TIPS) reduces portal pressure and may improve outcomes, but its role in patients receiving immunoncology-based systemic therapy remains unclear. NISTIPS TRITICC-4 is a prospective, multicentre, non-interventional cohort study conducted at up to 25 centers in Germany. A total of 350 adult patients with cirrhosis and unresectable or metastatic HCC receiving first-line atezolizumab plus bevacizumab will be enrolled. Patients are allocated to two cohorts: TIPS in situ plus atezolizumab and bevacizumab or atezolizumab plus bevacizumab alone, according to routine clinical practice.The primary endpoint is time to deterioration of liver function (TTDL), defined as persistent worsening of liver parameters for >4 weeks. Secondary endpoints include overall survival, time on treatment, overall response rate, time to new extrahepatic lesions or death, and safety with focus on bleeding and TIPS-related complications.Time-to-event endpoints will be analyzed using Kaplan-Meier methods and Cox models. Propensity score matching will be applied to adjust for confounding. Analyses are exploratory. This study will provide real-world evidence on the impact of TIPS in HCC patients receiving atezolizumab plus bevacizumab and may support more individualized management strategies in this high-risk population. www.clinicaltrials.gov identifier is NCT07365930.

Combination of oral fluoropyrimidines and EGFR-directed antibodies in frail patients with metastatic colorectal cancer: a systematic review.

Hasenburg Alena Annbalou AA, Stintzing Sebastian S, Stahler Arndt A

Evidence of treatment strategies in frail patients (i.e. not fit for combination therapies) with unresectable metastatic colorectal cancer (mCRC) is limited to dose-reduced doublet regimens or oral fluoropyrimidines (FP) with bevacizumab. We conducted a systematic review analyzing evidence for oral FPs with epidermal growth factor receptor (EGFR)-directed monoclonal antibodies for patients with RAS wild-type (WT) mCRC across treatment lines. We searched PubMed and Cochrane Library for phase II and phase III studies evaluating oral FPs (capecitabine, S-1 or trifluridine/tipiracil (FTD/TPI)) plus EGFR-directed monoclonal antibody (panitumumab or cetuximab) in mCRC. Outcomes included efficacy and safety. Seven publications met inclusion criteria (n = 262 patients). First-line data was limited to elderly cohorts receiving capecitabine plus cetuximab or panitumumab with a median progression-free survival (PFS)/median overall survival (OS) of 7.2/17.1 months (cetuximab) and 7.5/23.7 months (panitumumab), respectively. In third-line and beyond, median PFS for the combination of FTD/TPI plus cetuximab or panitumumab ranged from 2.4 (cetuximab) to 5.8 months (panitumumab), and OS from 9.8 (cetuximab) to 14.2 months (panitumumab). S-1 plus cetuximab was associated with a median PFS of 5.5 months and OS of 13.6 months. While capecitabine should not be used together with anti-EGFR antibodies, FTD/TPI in combination with an EGFR-directed antibody appears feasible, shows promising activity and manageable toxicity profile in RAS WT mCRC potentially offering an alternative for frail patients; prospective trials are needed.

CAPTYN, a Blood-Based Machine-Learning Model Predicting Clinical Benefit of Atezolizumab-Bevacizumab in Hepatocellular Carcinoma: Validation in the IMbrave150 Trial.

Jo Gae Hoon GH, Hwang Sohyun S, Scheiner Bernhard B, Woo Seonjeong S et al.

Later-line Treatment Selection in Metastatic Colorectal Cancer: Trifluridine/Tipiracil Plus Bevacizumab, Regorafenib, and Fruquintinib.

Sagawa Tamotsu T, Hirakawa Masahiro M, Nagashima Hiroyuki H, Fujikawa Koshi K

Later-line therapy for metastatic colorectal cancer (mCRC) increasingly requires selection among treatments with different mechanisms, toxicity profiles, and sequencing evidence. Trifluridine/tipiracil plus bevacizumab has robust randomized evidence from SUNLIGHT, but objective response remains uncommon and hematologic toxicity can limit treatment delivery in heavily pretreated patients. Regorafenib and fruquintinib are minimally myelosuppressive oral alternatives, yet they differ in dose strategy, hepatotoxicity, hand-foot skin reaction, hypertension, and proteinuria. This narrative review updates pivotal and recent evidence and proposes an evidence-informed framework that treats hematologic reserve as a clinical fitness construct rather than a fixed laboratory threshold. We additionally examine the clinical implications of low response rates, prior anti-angiogenic exposure, emerging molecular predictors including KRAS G12, evidence in older or vulnerable patients, and recent phase III developments. Current data do not support a validated molecular biomarker for choosing among these three options, and no randomized head-to-head comparison of regorafenib and fruquintinib exists. Accordingly, treatment selection should be individualized according to prior therapies, toxicity vulnerability, organ function, tumor tempo, and patient goals. Hypertension and proteinuria are important selection factors but may also be modifiable treatment-delivery factors. The proposed algorithms and adverse-event radar chart are intended as practical visual syntheses rather than validated guidelines or formal cross-trial comparisons.