Letter Regarding “Impact of Immune-Related Adverse Events on Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Hepatocellular Carcinoma”

Abstract

Immunologic checkpoint inhibitors (ICIs) have demonstrated efficacy in a variety of malignancies. Despite impressive therapeutic benefits, ICIs may induce profound immune-related adverse events (irAEs). While the occurrence of irAEs may implicate improved T cell activity, whether irAEs predicts anti-tumor immune responses remains controversial. The paper by Kennedy Yao Yi Ng et al. adds to the evidence of the impact of irAEs in advanced hepatocellular carcinoma, which demonstrated that multi-system involvement of irAEs positively correlated with treatment responses and survival. We are, however, concerned about the grouping method and potential statistical bias. Therefore, we listed a few questions and possible solutions under each circumstance, which we would like to share with authors and readers.

Biomarkers predicting the efficacy of immune checkpoint inhibitors in hepatocellular carcinoma

“…Another study involving 198 patients undergoing ICIs treatment found that the occurrence of grade ≥3 irAEs was associated with better survival compared to grades 1 and 2 (PFS: 8.5 months vs. 3.6 months vs. 1.3 months; OS: 26.9 months vs. 14.0 months vs. 4.6 months) (160). However, some concerns have been raised by other researchers regarding the grouping and statistical analysis methods employed in this study (161). Furthermore, in a multicenter study involving 268 patients treated with Atez/Bev, no significant differences were found in OS and PFS concerning irAEs (69).…”