Are anti-PD-1-associated immune related adverse events a harbinger of favorable clinical prognosis in patients with gastric cancer?

Abstract

Background Immune checkpoint inhibitors (ICIs) has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate immune related adverse events (irAEs) in patients. Some studies have shown that there is a close relationship between the occurrence of irAEs and prognosis. In present study, we have attempted to establish whether the occurrence of irAEs after the use of anti PD-1 antibodies is associated with treatment efficacy in people with advanced gastric cancer (AGC). Methods This study included patients treated with the anti-PD-1 antibodies for AGC patients at The Fourth Hospital of Hebei Medical University. IrAEs were identified clinically and graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.03. Efficacy was evaluated with objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS). The analysis was performed to determine the association between irAEs and clinical outcomes. Result Of the 74 AGC patients in our study, 24 developed irAEs. The DCR of the irAE displayed a trend better than that of non-irAE group but without statistical difference (41.70% VS 6.0%, p = 0.118). Median PFS in the irAE group was superior to that in the non-irAE group (176 days VS 94 days, p = 0.001). Median OS also showed this trend of difference at borderline statistical level (292 days VS 239 days, p = 0.057). Multivariate analysis also demonstrated irAE (HR = 0.269, 95%CI: 0.088 to 0.822, p = 0.021) were associated independently with the better prognosis for AGC patients. Conclusion In advanced gastric cancer treated with anti PD-1 antibodies, the occourence of irAEs might contribute to the improved prognosis.

Predictive Biomarkers for Immunotherapy in Gastric Cancer: Current Status and Emerging Prospects

“…Several studies have suggested a potential association between irAEs and a more favorable response to immunotherapy in patients [118,119]. Additionally, research has demonstrated a correlation between the occurrence of irAEs following immunotherapy and improved survival outcomes in GC patients [120][121][122]. Furthermore, certain studies have identified potential biomarkers for predicting the occurrence of irAEs [123].…”

Refining PD-1/PD-L1 assessment for biomarker-guided immunotherapy - a review

“…irAEs that occur early after treatment initiation are associated with favorable PFS and ORR in NSCLC patients treated with nivolumab [ 150 ]. Patients with gastric adenocarcinoma with irAEs treated with anti-PD-1 antibodies had a longer OS (176 days vs 94 days, P ═ 0.001) than patients without irAEs, and the occurrence of irAEs was an independent favorable prognostic factor in this group [ 152 ].…”

Immune-related adverse event-related adrenal insufficiency mediates immune checkpoint inhibitors efficacy for cancer treatment

“…IrAEs have been proven to promote the treatment e cacy of ICIs in patients with melanoma, NSCLC, hepatocellular carcinoma, and gastric cancer (Nakamura et al, 2017;Toi et al, 2018;Xu et al, 2021;Zhang et al, 2022). However, the relationship between irAE-related AI and ICIs treatment e cacy has not yet been evaluate owing to the low incidence and concealment of AI.…”