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

Abstract

BackgroundSeveral studies have reported an association between the occurrence of immune-related adverse events (irAEs) and prognosis in patients with melanoma treated with immune checkpoint inhibitors (ICIs), but the results remain controversial. We conducted a systematic review and meta-analysis to investigate the association between irAEs and survival in patients with melanoma treated with ICIs.MethodsWe searched the PubMed, Web of Science, and China National Knowledge Infrastructure databases through May 5, 2022 for clinical studies evaluating the association between irAEs and in melanoma patients treated with ICIs. Combined hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were calculated using fixed- or random-effects models based on heterogeneity. ResultsA total of 60 articles were included, with 16,520 patients. In patients with melanoma treated with ICIs, the occurrence of irAEs was significantly associated with better OS (HR, 0.58; 95% confidence interval [CI], 0.51–0.66; P<0.00001) and PFS (HR, 0.61; 95%CI, 0.51–0.72; P<0.00001). Endocrine irAEs (OS, HR, 0.81; 95%CI, 0.72–0.92; P=0.001; PFS: HR, 0.84; 95%CI, 0.73–0.96, P=0.009), skin irAEs (OS, HR, 0.59; 95%CI, 0.41–0.85; P=0.004; PFS: HR, 0.43; 95%CI, 0.36–0.52; P<0.00001), vitiligo (OS, HR, 0.22; 95%CI, 0.15–0.31; P<0.00001; PFS, HR, 0.33; 95%CI, 0.25–0.44; P<0.00001), and grade 1–2 irAEs (OS, HR, 0.67; 95%CI, 0.58–0.78; P<0.00001; PFS, HR, 0.62; 95%CI, 0.51–0.76; P<0.00001) showed similar results. However, thyroid, lung, gastrointestinal, liver, and grade 3–4 irAEs were not significantly associated with OS and PFS. The occurrence of non-thyroid endocrine irAEs was significantly associated with better OS (HR, 0.22; 95%CI, 0.15–0.31; P<0.00001). In patients with melanoma treated with anti-programmed cell death protein 1 (OS, HR, 0.61; 95%CI, 0.51–0.72; P<0.00001; PFS, HR, 0.59; 95%CI, 0.47–0.74; P<0.00001), the association between irAEs and clinical benefit was clearer than in patients treated with anti-cytotoxic T-lymphocyte-associated protein 4 (OS, HR, 0.68; 95%CI, 0.52–0.89; P=0.005; PFS, HR, 0.93; 95%CI, 0.49–1.78; P=0.83).ConclusionAmong patients with melanoma treated with ICIs, those who developed non-thyroid endocrine irAEs and cutaneous irAEs have better prognosis. This suggests that non-thyroid endocrine irAEs and cutaneous irAEs may be a prognostic biomarker for patients with melanoma treated with ICIs.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022338308.

Association of the CD4+ /CD8+ ratio with response to PD-1 inhibitor-based combination therapy and dermatologic toxicities in patients with advanced gastric and esophageal cancer

“…In this study, 33.3% and 31.3% of patients were with dermatologic toxicities in the training cohort and validation cohort, respectively. Previous studies showed that dermatologic toxicities may be associated with positive antitumor response [50]. In this study, we found although dermatologic toxicities is not an independent prognostic factor for patients with advanced GC and EC treated with PD-1 inhibitor-based combination therapy, it is signi cantly correlated with their OS (P < 0.001).…”

Cutaneous Adverse Events and Cancer Survival Prognosis With Immune Checkpoint Inhibitor Treatment

“…Hence, the emergence of cirAEs can serve as a prognostic factor for patients with cancer undergoing ICI treatment. 2, [35][36][37][38] Additionally, to minimize potential bias associated with the varying durations of ICI exposure, we performed a landmark analysis for both PFS and OS among patients with a minimum exposure period of 6 weeks. The findings supported the hypothesis that the presence of cirAEs is associated with long-term therapeutic advantages (PFS and OS) among patients treated with ICIs.…”

“…These findings are consistent with previous meta-analyses that reported an association between cirAE prevalence and improved PFS and OS. Hence, the emergence of cirAEs can serve as a prognostic factor for patients with cancer undergoing ICI treatment . Additionally, to minimize potential bias associated with the varying durations of ICI exposure, we performed a landmark analysis for both PFS and OS among patients with a minimum exposure period of 6 weeks.…”

Frequency and characteristics of immune-related thyroid adverse events in patients with resected stage III/IV melanoma treated with adjuvant PD-1 inhibitors: a national cohort study

“…Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and improved the treatment of patients with melanoma [ 1 ]. The most important immune checkpoint targets are cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1).…”

“…Most irAEs appear within the first weeks to 3 months after initiation of ICIs [ 5 , 6 ], and female sex and younger age seem to be associated with higher rates of irAEs [ 7 , 8 ]. Previous studies have shown that irAEs predict improved tumor response and overall survival in metastatic cancer patients treated with ICIs [ 1 , 5 , 9 ].…”