Patient Selection and Contraindications for Immunotherapy in Unresectable HCC

Selecting appropriate immunotherapy regimens for people with unresectable hepatocellular carcinoma (HCC) requires careful consideration of contraindications and patient-specific factors. Mahipal explains that approximately half of patients have soft contraindications to at least 1 first-line option. For atezolizumab-bevacizumab, the bevacizumab component creates concerns for patients with recent massive bleeding, variceal hemorrhage, tumor rupture with peritoneal bleeding, uncontrolled hypertension, or recent coronary or cerebrovascular events. The availability of dual checkpoint inhibitors now provides alternatives for these situations.

Conversely, dual checkpoint inhibitor regimens carry higher risks for people with autoimmune conditions, even when controlled enough to permit single-agent immunotherapy. The risk of disease flare increases substantially with dual immunotherapy compared with single-agent PD-1 inhibitors. Yarchoan notes that access to esophagogastroduodenoscopy also influences treatment selection—atezolizumab-bevacizumab requires recent endoscopy to assess variceal risk, which may delay treatment initiation. Nivolumab-ipilimumab can be started immediately, making it advantageous for people with rapidly progressive disease requiring urgent intervention.

Response rate considerations may guide selection for specific clinical scenarios. For patients with massive tumor burden who likely need immediate response and may only tolerate 1 line of therapy, the higher response rates with atezolizumab-bevacizumab or nivolumab-ipilimumab (27%-36%) may be preferred. For those with lower tumor burden and indolent disease who will likely receive multiple therapy lines, the response rate becomes less critical. Treatment decisions must balance efficacy data, toxicity profiles, contraindications, and individual patient circumstances to optimize outcomes while minimizing harm.