Caution: bevacizumab-based regimens with untreated varices

This caution concerns atezolizumab with bevacizumab, the standard first-line regimen in hepatocellular carcinoma, in patients whose liver disease, often from hepatitis B or C, has produced untreated oesophageal varices. VEGF blockade impairs mucosal healing and worsens the effects of portal pressure, and cirrhotic patients commonly have varices, so the anti-VEGF component can cause fatal variceal bleeding. IMbrave150 required endoscopy within six months of enrolment and treatment of any varices found, and upper gastrointestinal bleeding was still observed on atezolizumab-bevacizumab; the trial protocols and label warnings are the evidence. For patients at high bleeding risk, the durvalumab-based STRIDE regimen tested in HIMALAYA, or nivolumab with ipilimumab, are alternatives.