The association between immune-related adverse events and the prognosis of solid cancer patients treated with immunotherapy: a systematic review and meta-analysis

Abstract

Background: Immune-related adverse events (irAEs) are common during immune checkpoint inhibitor (ICI) treatment and reported to be associated with good survival. This study evaluated the association between onset timing of irAEs and survival of cancer patients treated with ICIs. Methods: Databases including PubMed, Embase, and the Cochrane library were systematically searched to retrieve clinical studies assessing the relationship between irAEs and survival in cancer patients with ICIs. The overall response rate for treatment response and hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were calculated using RevMan 5.3. Subgroup analysis in terms of cancer type, ICIs type, region, specific irAEs, accordingly. Results: A total of 34 studies were included. The HRs for OS and PFS in cancer patients with versus without irAEs were 0.57 [95% confidence interval (CI): 0.44, 0.74; p < 0.0001], and 0.50 (95% CI: 0.37, 0.67; p < 0.00001), respectively. The odds ratio for overall response in cancer patients with irAEs was 4.72 (95% CI: 3.48, 6.40; p < 0.00001) compared with those without irAEs. Subgroup analyses suggested that the prognostic role of irAEs was associated with cancer types and region, but not irAEs types. The landmark analysis of OS revealed that there is a non-proportional (early) effect of irAEs on OS in ICI-treated cancer patients (landmark >12 weeks, HROS = 1.08; 95% CI: 0.89, 1.30; p = 0.46). Conclusion: Our findings suggest that the occurrence of irAEs could be a prognostic factor for cancer patients who were treated with ICIs.

Patients with melanoma treated with immune checkpoint inhibitors who had non-thyroid endocrine and skin immune-related adverse events have better prognosis: A systematic review and meta-analysis

“…The lack of statistical significance in OS and PFS among patients with melanoma with grade 3 and above irAEs may be due to the increased mortality associated with higher side effects or glucocorticoid therapy. Our conclusions are consistent with previously published meta-analyses of all patients with cancer, suggesting a positive association between the occurrence of irAEs and PFS and OS, and the occurrence of irAEs may be a prognostic factor for patients with cancer treated with ICIs ( 19 – 23 , 86 ). Several studies have also found that the occurrence of low-grade irAEs, but not severe irAEs, is associated with better ICI outcomes in patients with cancer ( 19 , 23 , 88 ).…”

“…A total of 57 articles assessed the association between the occurrence of irAEs and OS in patients with melanoma ( 13 – 18 , 32 – 39 , 41 – 58 , 60 – 71 , 73 – 75 , 77 – 86 ), and 34 assessed PFS ( 14 , 15 , 18 , 32 , 34 , 36 – 42 , 47 , 49 , 54 , 55 , 58 – 60 , 62 , 64 , 66 , 68 – 72 , 75 , 76 , 78 , 79 , 81 , 82 , 85 ). Among these, the study of Abu-Sbeih et al.…”

Comparison of vonoprazan and proton pump inhibitors for the treatment of gastric endoscopic submucosal dissection-induced ulcer: an updated systematic review and meta-analysis

“…With respect to AEs, our meta-analysis showed that vonoprazan had a significantly lower rate of adverse events than did PPIs. In contrast, the meta-analysis conducted by Xu et al [37] demonstrated that the incidence of adverse events was similar between vonoprazan and PPIs (P = 0.66). There are several differences between our meta-analysis and that of Xu et al [37] Only RCTs were included in our meta-analysis, while RCTs and cohort and single-arm studies were included in the meta-analysis by Xu et al [37] In addition, only patients with gastric ESD-induced ulcers were included in our meta-analysis, while patients with H. pylori infection, gastroesophageal reflux disease, peptic ulcer disease and ESD-induced ulcers were included in the meta-analysis by Xu et al [37] Notably, only seven RCTs were included for the comparison of adverse events in our meta-analysis.…”

A Phase 2 Clinical Trial of Combination Nivolumab, Ipilimumab, and Paclitaxel in Patients With Untreated Metastatic NSCLC: The OPTIMAL Trial

“…17 Furthermore, there is ample published evidence that development of endocrinopathy, including thyroid dysfunction and hypophysitis, on immune checkpointbased treatment is predictive of improved survival for patients. 18,19 Most recently, a pooled analysis of combination chemotherapy with atezolizumab revealed that lower grade (1-2) toxicity in general was associated with OS benefit. 20 Ultimately, given the limited sample size in our study, it remains challenging to draw conclusions regarding specific toxicity rates from cross-trial comparisons.…”