Dataset Information

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

ABSTRACT:

Background and objective

Although 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.

Methods

Various 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.

Results

A 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.

Conclusions

In 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.

SUBMITTER: Zhao Z

PROVIDER: S-EPMC8479111 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVE:To evaluate rates of serious organ specific immune-related adverse events, general adverse events related to immune activation, and adverse events consistent with musculoskeletal problems for anti-programmed cell death 1 (PD-1) drugs overall and compared with control treatments. DESIGN:Systematic review and meta-analysis. DATA SOURCES:Medline, Embase, Cochrane Library, Web of Science, and Scopus searched to 16 March 2017 and combined with data from ClinicalTrials.gov. STUDY SELECTION:Eligible studies included primary clinical trial data on patients with cancer with recurrent or metastatic disease. DATA EXTRACTION:Three independent investigators extracted data on adverse events from ClinicalTrials.gov and the published studies. Risk of bias was assessed using the Cochrane tool by three independent investigators. RESULTS:13 relevant studies were included; adverse event data were available on ClinicalTrials.gov for eight. Studies compared nivolumab (n=6), pembrolizumab (5), or atezolizumab (2) with chemotherapy (11), targeted drugs (1), or both (1). Serious organ specific immune-related adverse events were rare, but compared with standard treatment, rates of hypothyroidism (odds ratio 7.56, 95% confidence interval 4.53 to 12.61), pneumonitis (5.37, 2.73 to 10.56), colitis (2.88, 1.30 to 6.37), and hypophysitis (3.38, 1.02 to 11.08) were increased with anti-PD-1 drugs. Of the general adverse events related to immune activation, only the rate of rash (2.34, 2.73 to 10.56) increased. Incidence of fatigue (32%) and diarrhea (19%) were high but similar to control. Reporting of adverse events consistent with musculoskeletal problems was inconsistent; rates varied but were over 20% in some studies for arthraligia and back pain. CONCLUSIONS:Organ specific immune-related adverse events are uncommon with anti-PD-1 drugs but the risk is increased compared with control treatments. General adverse events related to immune activation are largely similar. Adverse events consistent with musculoskeletal problems are inconsistently reported but adverse events may be common.

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