肝細胞癌における重度の免疫関連有害事象を軽減するための予防的コルチコステロイドの再検討

Dual immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) or its ligand (PD-L1) have reshaped the treatment landscape of unresectable hepatocellular carcinoma (HCC). However, their clinical uptake remains limited by frequent severe immune-related adverse events (irAEs), underscoring the urgent need for effective prophylactic strategies. Corticosteroids are traditionally viewed as antagonistic to antitumor immunity and have long been prohibited from prophylactic use in ICI-only regimens. Yet this dogma is increasingly at odds with both practice and evidence. Prophylactic corticosteroids (PC) are routinely administered in lung cancer patients receiving immunochemotherapy, primarily to prevent chemotherapy-related toxicity. In this context, PC have been associated with reduced severe irAEs without compromising efficacy. Our preclinical HCC studies demonstrate that corticosteroid premedication does not impair T-cell activation or antitumor activity induced by dual ICI therapy. Emerging clinical data likewise demonstrate no detrimental impact of baseline or concomitant corticosteroids on oncological outcomes in HCC. In this Expert Opinion, we contend that it is time to rethink the long-standing prohibition of PC in ICI-based treatment. Judicious PC use may offer a practical means to mitigate severe irAEs-particularly in anti-CTLA-4-containing regimens-while maintaining antitumor activity. We advocate for prospective evaluation of PC in ICI-based combinations with higher immune-mediated toxicity to better define their role in HCC.