A correlation analysis between immune-related adverse events and the curative effect caused by immune checkpoint inhibitors on patients with advanced primary Hepatocellular carcinoma

Abstract

Abstract: Objective To explore the relationship between immune-related adverse events (irAEs) in patients with advanced primary liver cancer during anti-PD-1/PD-L1 treatment and the efficacy of immunotherapy, and to provide clinical evidence for clarifying their correlation.Methods Between January 2019 and January 2022, eighty patients with advanced primary liver cancer were treated with PD-1/PD-L1 inhibitors alone or in combination, and the included cases met the requirements. The efficacy of PD-1/PD-L1 inhibitor was evaluated after treatment, and the irAEs and its severity during immunotherapy were evaluated according to the evaluation standard of common adverse events (CTCAE version 5.0).Results The immune checkpoint inhibitors (ICIs) used in these 80 patients with advanced primary liver cancer were Tereplizumab, Karelizumab, Cindilizumab and Pabolizumab. During the immunotherapy, 45 patients (56.2%) had 63 times of irAEs, of which 8 patients (10.0%) reported 11 times of irAEs ≥3, and the median time from ICIs treatment to the present of irAEs was 2.4 months. The common irAEs were reactive cutaneous capillary hyperplasia (23 times, 36.5%), rash/vitiligo (14 times, 22.2%), hypothyroidism (10 times, 15.9%), hepatitis (6 times, 9.5%), pancreatic injury (3 times, 4.8%), pneumonia (3 times, 4.8%) and diarrhea/colitis (2 times). In 45 patients with irAEs, complete response (CR), partial response (PR), stable disease (SD) and porgressive disease (PD) were 0 (0%), 18 (40.0%), 19 (42.2%) and 8 (17.8%), respectively. In 35 patients without irAEs, CR was 1 (2.8%) and PR was 5 (14.3%). The Objective response rate (ORR) of patients with and without irAEs was 40.0% (18/45) and 14.3% (5/35) respectively, and the difference was statistically significant (P<0.05). The disease control rate (DCR) of patients with and without irAEs was 82.2% (37/45) and 42.9% (15/35) respectively, and the difference was statistically significant (P<0.05). All cases were followed up, and the median follow-up time was 10.5 months. By the end of the follow-up, the median progression-free survival (PFS) of patients with and without irAEs was 10.4 months and 4.3 months, respectively, and the difference was statistically significant (P<0.05). The median overall survival (OS) of patients with and without irAEs was 17.6 months and 8.8 months, respectively, and the difference was statistically significant (P<0.05).Conclusion For patients with advanced primary liver cancer, treatment with PD-1/PD-L1 inhibitors shows good efficacy and safety. Meanwhile, there is a correlation between the occurrence of irAEs and the efficacy and clinical outcome of immunotherapy; thus, it is a potential marker to predict the efficacy.

Key words: Advanced primary Hepatocellular carcinoma, Immune checkpoint inhibitors, Immune-related adverse events

HU Zhi-qiang, MEN Fen-yong, LIU Dong. A correlation analysis between immune-related adverse events and the curative effect caused by immune checkpoint inhibitors on patients with advanced primary Hepatocellular carcinoma[J]. Chinese Hepatolgy, 2023, 28(8): 935-937.

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