Thyroid function abnormality induced by PD-1 inhibitors have a positive impact on survival in patients with non-small cell lung cancer

Zhou, Yuwen; Xia, Rong; Xiao, Huilang; Pu, Dan; Long, Yi-Xiu; Ding, Zhenyu; Liu, Jiyan; Ma, Xuelei

doi:10.1016/j.intimp.2020.107296

Cited by 26 publications

(17 citation statements)

References 29 publications

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“…In any case, thyroid autoimmunity in cancer patients treated with ICPIs is worth further investigation, in view of published findings suggesting a more favorable outcome in patient who develop autoimmune features during therapy with immunomodulatory agents (i.e., interferon or GVAX) [ 29 , 30 ]. With regard to ICPIs, a few studies suggested a better outcome in those patients, in which a thyroid dysfunction occurred during treatment with anti PD-1 or anti PD-L1 molecules, in contrast to our findings [ 31 – 33 ]. However, a clear relationship with thyroid autoimmunity was not demonstrated.…”

Section: Discussioncontrasting

confidence: 99%

Endocrine-related adverse events in a large series of cancer patients treated with anti-PD1 therapy

et al. 2021

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Purpose Immune checkpoint inhibitors have opened a new scenario in the treatment of cancer. These agents can elicit adverse events, which may affect different systems and organs, including the endocrine system. The aims of this study were to evaluate the impact of the anti-PD-1 molecules nivolumab and pembrolizumab on endocrine toxicity and on patient outcome. Methods A retrospective and multicentre study was designed, which involved a total of 251 patients affected by different tumors (mostly non-small cell lung cancer, 68.92% and melanoma, 24.30%) and treated with the PD-1 inhibitors nivolumab (61.35%) or pembrolizumab (38.65%) for up to 60 months. Clinical and biochemical data were recorded until July 31, 2020. Results Endocrine toxicity occurred in 70 out of 251 patients (27.89%). It was mostly related to thyroid dysfunction and in 75% of cases occurred within 6 months from the beginning of therapy. A previous endocrine morbidity and female gender were predictors of endocrine toxicity. There was no association between endocrine dysfunction and patient outcome. However, when all toxicities (i.e., endocrine and non endocrine) were considered, a significant association with progression-free survival and overall survival was found. Conclusions Thyroid alterations are frequently observed in cancer patients treated with anti PD-1 drugs, particularly in women and in the presence of a previous endocrinopathy. We suggest that regular thyroid assessment should be performed in these patients, especially in the first months of therapy. Finally, the onset of side effects, related to anti PD-1 agents, appears to be associated with a better outcome.

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Section: Discussioncontrasting

confidence: 99%

Endocrine-related adverse events in a large series of cancer patients treated with anti-PD1 therapy

et al. 2021

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“…The full text of the remaining 42 studies was further assessed for eligibility, and 17 additional publications were excluded. Eventually, 25 articles, including 8,452 patients with confirmed NSCLC receiving anti-PD-1 treatment, were enrolled in our meta-analysis ( 13 , 16 – 39 ). The process of study selection is illustrated in Figure 1 .…”

Section: Resultsmentioning

confidence: 99%

“…To further investigate the influence of different AEs, we performed subgroup analyses for pulmonary, skin, and endocrine irAEs. In addition to the aforementioned eight studies of specific irAEs ( 17 , 20 , 22 , 23 , 25 , 27 , 33 , 39 ), we also extracted survival data from the other five articles that reported HRs for these three AEs ( 13 , 16 , 21 , 24 , 34 ). The analysis revealed that skin (HR: 0.41; 95% CI: 0.32–0.52; P < 0.01) and endocrine (HR: 0.41; 95% CI: 0.33–0.51; P < 0.01) irAEs were significantly associated with longer OS, whereas pulmonary irAEs showed no correlation (HR: 0.98; 95% CI: 0.53–1.83; P = 0.96) ( Figure 4A ).…”

Section: Resultsmentioning

confidence: 99%

“…As described in the included studies, patients with common skin irAEs may develop some symptoms like immune-related pruritus, rash, and erythema ( 24 , 34 ), which can be easy to identify. Some endocrine irAEs following anti-PD-1 therapies include hyper/hypothyroidism with two or more abnormal thyroid function tests (free thyroxine, free triiodothyronine, and thyroid stimulating hormone) ( 39 ), and adrenal insufficiency diagnosed by an adrenocorticotropic hormone stimulation test ( 57 ). Once irAEs are identified in a patient, appropriate and prompt management can be carried out in a timely manner to improve patient outcomes.…”

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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“…Hypothyroidism has also been observed to inhibit tumour growth and prolong survival in patients with nonsmall cell lung cancer. 35 Combination therapy using PD-1 and thyroid inhibitors is viewed as an effective therapeutic strategy that is associated with favourable prognosis in patients without hypothyroidism. In our study, we performed subgroup analysis in hypothyroidism group and observed that PFS was longer in patients with preimmunotherapy hypothyroidism (six patients) achieved than those without hypothyroidism; however, the difference was statistically nonsignificant.…”

Section: Lee Et Al Retrospectively Investigated 45 Patients With Solidmentioning

confidence: 99%

Hypothyroidism is a predictive factor of superior antitumour efficacy of programmed death 1 inhibitors in hepatocellular carcinoma

Leng

Chen

et al. 2021

Intl Journal of Cancer

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Thyroid function abnormality induced by PD-1 inhibitors have a positive impact on survival in patients with non-small cell lung cancer

Cited by 26 publications

References 29 publications

Endocrine-related adverse events in a large series of cancer patients treated with anti-PD1 therapy

Endocrine-related adverse events in a large series of cancer patients treated with anti-PD1 therapy

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

Hypothyroidism is a predictive factor of superior antitumour efficacy of programmed death 1 inhibitors in hepatocellular carcinoma

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