Successful Sequential Immunotherapy for Multiple Primary Malignancies (Unresectable Hepatocellular Carcinoma and...

Hepatocellular carcinoma and esophageal squamous cell carcinoma are aggressive malignancies, and their coexistence presents a significant treatment challenge. We herein report a rare case of multifocal hepatocellular carcinoma and esophageal squamous cell carcinoma that was successfully treated with sequential immune checkpoint inhibitors. Atezolizumab plus bevacizumab led to tumor regression, but following a brain infarction, the therapy was switched to durvalumab plus tremelimumab, and durable remission was achieved despite programmed death-ligand 1 (PD-L1) negativity. This case underscores the potential application of immune checkpoint inhibitors (ICIs) in the treatment of multiple primary malignancies and highlights the need for further research on predictive biomarkers and optimal combination strategies. This case also raises important questions regarding the mechanisms of ICI efficacy in PD-L1-negative malignancies, and suggests that immune synergy between coexisting tumors may enhance antitumor responses.