The role of systemic chemotherapy after immunotherapy failure in advanced hepatocellular carcinoma (HCC) remains poorly defined. We describe five patients with advanced HCC who progressed on immune checkpoint inhibitor–based therapy and subsequently received cytotoxic chemotherapy. Gemcitabine-, fluorouracil-, and platinum-based chemotherapy regimens, including hepatic arterial infusion chemotherapy in one patient, were administered.

Three patients achieved a partial radiologic response, whereas two showed early disease progression. These descriptive observations suggest that, in carefully selected patients with preserved liver function and good performance status, chemotherapy may be associated with radiologic disease control after immunotherapy failure.