Anti-PD-1/L1-associated immune-related adverse events as harbinger of favorable clinical outcome: systematic review and meta-analysis

Park, Robin; Lopes, Laercio; Saeed, Anwaar

doi:10.1007/s12094-020-02397-5

Cited by 34 publications

(25 citation statements)

References 52 publications

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“…To avoid such heterogeneity and improve study comparability, we focused our analysis on patients with NSCLC treated with anti-PD-1 antibodies. Consistent with the subgroup analysis results of NSCLC from other systematic reviews ( 11 , 51 , 52 ), our research revealed that the occurrences of irAEs in patients with NSCLC treated with anti-PD-1 antibodies were closely associated with improved clinical outcomes, including OS, PFS, ORRs, and DCRs. Our results demonstrated that patients with NSCLC who developed any irAE after anti-PD-1 treatment showed a 50% reduction in the risks of death and disease progression compared to those without any AEs related to ICIs.…”

Section: Discussionsupporting

confidence: 90%

“…Fausto et al ( 11 ) included 10 studies regarding NSCLC patients receiving anti-PD-1 treatments in an overall systematic review of solid tumors. Besides, Park et al ( 52 ) concluded the predictive effects of anti-PD-1/L1-associated irAEs for favorable clinical outcomes in a recent systematic review, which only covered 11 studies of NSCLC treated with anti-PD-1 regimens. Recently, Wang et al ( 60 ) reported that irAEs in lung cancer might predict better ICI efficacy, in which 17 lung cancer cohorts treated with anti-PD-1 regimens were included.…”

Section: Discussionmentioning

confidence: 99%

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Immune-Related Adverse Events Associated With Outcomes in Patients With NSCLC Treated With Anti-PD-1 Inhibitors: A Systematic Review and Meta-Analysis

Zhao

Wang

et al. 2021

Front. Oncol.

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Background and ObjectiveAlthough anti-programmed cell death protein 1 (PD-1) antibodies have exerted remarkable anticancer activity in non-small cell lung cancer (NSCLC), it remains a challenge to identify patients who can benefit from these treatments. Immune-related adverse events (irAEs) may be associated with improved clinical outcomes after immune checkpoint inhibition. However, no conclusive evidence of this correlation has been summarized in patients with NSCLC receiving PD-1 inhibitors. We performed a systematic review and meta-analysis to evaluate the association between irAEs induced by anti-PD-1 antibodies and clinical outcomes in patients with NSCLC.MethodsVarious databases were searched from their inception to January 9, 2021, followed by screening of eligible studies. Hazard ratios were used for the pooled analysis of overall survival (OS) and progression-free survival (PFS), while odds ratios (ORs) were utilized to pool objective response rates (ORRs) and disease control rates (DCRs). A random-effects model was applied to all analyses.ResultsA total of 26 cohorts, including 8,452 patients with NSCLC receiving anti-PD-1 antibodies, were enrolled in the study. Significantly improved OS (HR: 0.51; 95% CI: 0.44-0.60; P < 0.01) and PFS (HR: 0.50; 95% CI: 0.43-0.58; P < 0.01) were found to be correlated with irAEs. In addition, patients with NSCLC who developed irAEs after PD-1 inhibition demonstrated better responses to therapies, confirmed by pooled ORs of ORRs (OR: 3.41; 95% CI: 2.66-4.35; P < 0.01) and DCRs (OR: 4.08; 95% CI: 2.30-7.24; P < 0.01). Furthermore, subgroup analysis suggested that both skin and endocrine irAEs are closely correlated with a reduced risk of death, whereas pulmonary irAEs showed no association with longer OS.ConclusionsIn patients with NSCLC treated with anti-PD-1 therapies, the presence of irAEs was strongly correlated with better survival and response, suggesting its potential role as a predictive biomarker for outcomes after PD-1 inhibition.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Immune-Related Adverse Events Associated With Outcomes in Patients With NSCLC Treated With Anti-PD-1 Inhibitors: A Systematic Review and Meta-Analysis

Zhao

Wang

et al. 2021

Front. Oncol.

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“…Meanwhile, there is increasing concern regarding immunerelated adverse events (irAEs) of ICIs (12)(13)(14). The appearance of some irAEs have beenshown to be related to the efficacy of ICI agents in patients with NSCLC and melanoma (15,16), but this relationship has not been established in patients with SCLC. SCLC is characterized by complex immunophenotypes, and autoimmune-related paraneoplastic syndromes are commonly reported among SCLC patients (17).…”

Section: Introductionmentioning

confidence: 99%

Immune Check Point Inhibitors and Immune-Related Adverse Events in Small Cell Lung Cancer

Hou

Zhou

et al. 2021

Front. Oncol.

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Small cell lung cancer (SCLC) is a malignant solid tumor. In recent years, although immune check point inhibitors (ICIs) have achieved important advances in the treatment of SCLC, immune-related adverse events (irAEs) have occurred at the same time during the therapeutic period. Some irAEs lead to dose reduction or treatment rejection. The immune microenvironment of SCLC is complicated, therefore, understanding irAEs associated with ICIs is of great importance and necessity for the clinical management of SCLC. However, the lack of comprehensive understanding of irAEs in patients with SCLC remains remarkable. This review aims to provide an up-to-date overview of ICIs and their associated irAEs in patients with SCLC based on present clinical data.

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“…Finally, associations between ICI‐triggered irAEs and favorable cancer treatment outcomes have been observed 11 . However, the extent (>30% of total body surface area) and severity of lesions in the present case necessitated immunotherapy discontinuation, with patient demise occurring soon thereafter.…”

Section: Discussionmentioning

confidence: 68%

Linear IgA/IgG bullous dermatosis after nivolumab therapy

et al. 2021

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Anti-PD-1/L1-associated immune-related adverse events as harbinger of favorable clinical outcome: systematic review and meta-analysis

Cited by 34 publications

References 52 publications

Immune-Related Adverse Events Associated With Outcomes in Patients With NSCLC Treated With Anti-PD-1 Inhibitors: A Systematic Review and Meta-Analysis

Immune-Related Adverse Events Associated With Outcomes in Patients With NSCLC Treated With Anti-PD-1 Inhibitors: A Systematic Review and Meta-Analysis

Immune Check Point Inhibitors and Immune-Related Adverse Events in Small Cell Lung Cancer

Linear IgA/IgG bullous dermatosis after nivolumab therapy

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