Immune-Related Adverse Events Predict the Efficacy of Immune Checkpoint Inhibitors in Lung Cancer Patients: A Meta-Analysis

Wang, Donghui; Chen, Cen; Gu, Yanli; Lu, Wanjun; Zhan, Ping; Liu, Hongbing; Lv, Tangfeng; Song, Yong; Zhang, Fang

doi:10.3389/fonc.2021.631949

Cited by 40 publications

(55 citation statements)

References 56 publications

(24 reference statements)

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“…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. Compared to these published reviews, we added approximately 9 more cohorts for meta-analysis, making our review more comprehensive and persuasive.…”

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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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: 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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“…[16] NSCLC is classi ed as a high tumor mutational burden cancer. [17] During or after immunotherapy, patients may experience immune-related adverse events (irAEs), in addition to commonly reported treatment-related side effects. [17] Although patients' assessments of the incidence and consequences of these irAEs are important, existing cancer-speci c PRO instruments [18,19] were not designed to capture irAEs, and may not fully re ect the bene ts and toxicity pro les of immunotherapies.…”

Section: Discussionmentioning

confidence: 99%

“…[17] During or after immunotherapy, patients may experience immune-related adverse events (irAEs), in addition to commonly reported treatment-related side effects. [17] Although patients' assessments of the incidence and consequences of these irAEs are important, existing cancer-speci c PRO instruments [18,19] were not designed to capture irAEs, and may not fully re ect the bene ts and toxicity pro les of immunotherapies. Clinical trial guidelines that promote transparent and accurate reporting of PROs, in an effort to facilitate interpretation of these complex data and their limitations, are further compounded by factors such as the unblinded nature of the NSCLC clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Immune-Checkpoint Inhibitors For The Treatment Of Non-Small Cell Lung Cancer: A Comparison Of The Regulatory Approvals In Europe And The United States

Zaim

Redekop

Groot

2022

Preprint

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The process of regulatory authorization of oncology drugs, including immune-checkpoint inhibitors, has been improved by the cooperation and coordination among the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Regulatory decisions of immune-checkpoint inhibitors by these agencies are often based on enhanced efficacy and acceptable toxicity profiles, investigated in randomized, open-label, clinical trials. In this study, we addressed the differences in regulatory approvals between the FDA and the EMA for immune-checkpoint inhibitors in the treatment of non-small cell lung cancer, from year 2015 until 2021; by focusing on: (1) time to approval of immune-checkpoint inhibitors, and (2) the considerations of patient-reported outcomes (PROs) by each agency. Both the FDA and the EMA recognize the value of PROs as important patient-centered endpoints when determining the efficacy of therapies, and considering drugs for approval. Despite similarities in the regulatory pathways and assessments used for immune-checkpoint inhibitor approvals, there are differences between the two agencies when time to approval or marketing authorization for these drugs were compared. Efforts to align regulatory practices, with high concordance approval outcomes, can lead to better use of resources associated with drug development. These efforts can also provide a more streamlined and predictable process for evaluation of the efficacy, safety and PRO measures for new immune-checkpoint inhibitors or disease indications. Further harmonization and collaboration between the EMA and the FDA on the PRO instrument development, measurement and validation are encouraged to increase the efficiency of the decision-making processes in the future.

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“…Interestingly, the genetic risk for hypothyroidism was associated with risk of developing thyroid immune-related adverse events in NSCLC (34). Furthermore, the occurrence of gastrointestinal, dermatological, and endocrine irAEs in lung cancer patients has been proven to be a predictor of enhanced immune checkpoint inhibitor efficacy (35).…”

Section: Endocrinopathymentioning

confidence: 99%

Management of Immune-Related Adverse Events in Patients With Non-Small Cell Lung Cancer

Burke

Rashdan

2021

Front. Oncol.

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With proven efficacy of the use of immunotherapy in almost all stages of NSCLC, immunotherapy toxicity has become a very important topic that requires immediate recognition and management. The diagnosis of toxicities associated with immunotherapy in lung cancer can be very challenging and often requires multidisciplinary effort. This mini review gives an overview of the diagnosis and management of immune-related adverse events that arise from using immunotherapy in NSCLC, as well as the potential biomarkers for its early identification and future directions.

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Immune-Related Adverse Events Predict the Efficacy of Immune Checkpoint Inhibitors in Lung Cancer Patients: A Meta-Analysis

Cited by 40 publications

References 56 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-Checkpoint Inhibitors For The Treatment Of Non-Small Cell Lung Cancer: A Comparison Of The Regulatory Approvals In Europe And The United States

Management of Immune-Related Adverse Events in Patients With Non-Small Cell Lung Cancer

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