Prognostic impact of thyroid dysfunctions on progression-free survival in patients with metastatic melanoma treated with anti-PD-1 antibodies

Frelau, Alexandra; Jali, E.; Campillo‐Gimenez, Boris; Pracht, Marc; Porneuf, M.; Dinulescu, M.; Edeline, Julien; Boussemart, Lise; Lesimple, Thierry

doi:10.1097/cmr.0000000000000739

Cited by 8 publications

(9 citation statements)

References 44 publications

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“…In addition, patients with NSCLC, renal cell carcinoma and metastatic melanoma who received PD-1 inhibitors and acquired overt thyroid dysfunction exhibited improved OS and PFS than those without thyroid dysfunction ( 17 ). In the present study, general, thyroid dysfunction was associated with a longer PFS in Chinese patients receiving PD-1 inhibitors, which was similar to previous studies focusing of Caucasian cancer patients receiving PD-1 inhibitors ( 23 , 24 ). Thus, it could be deduced that the prognostic value of thyroid dysfunction was not affected by ethnicity, although further studies should verify this hypothesis.…”

Section: Discussionsupporting

confidence: 91%

Thyroid dysfunction during PD‑1 inhibitor treatment in patients with cancer: Incidence and association with progression‑free survival

Wu¹,

Wang²,

Bai

et al. 2022

Oncol Lett

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The use of programmed cell death-1 (PD-1) inhibitors has recently been approved in China. As a consequence, the identification of relevant prognostic markers that can assess the efficacy of these compounds is required. Therefore, the present study aimed to explore the incidence of thyroid dysfunction and its ability to predict progression-free survival (PFS) in Chinese patients with cancer who received PD-1 inhibitor treatment. Data from 72 patients with cancer who received treatment with PD-1 inhibitors alone or in combination with chemotherapy or targeted drugs were analyzed. Moreover, the expression levels of free triiodothyronine, thyroxine, and thyrotropin during treatment were assessed to evaluate thyroid dysfunction. A total of 26 (36.1%) patients who had received PD-1 inhibitors developed thyroid dysfunction. Specifically, the incidence of thyroid dysfunction was 35.6% in patients with lung cancer, 25.0% in patients with malignant melanoma, and 46.7% in patients with other types of cancer. In addition, the median PFS was 7.0 (95% confidence interval, 4.9-9.1) months, whereas the 1-and 2-year PFS rates were 35.1 and 26.2%, respectively. Generally, patients with thyroid dysfunction exhibited longer PFS compared with those without thyroid dysfunction (P=0.001). Subgroup analyses were subsequently performed, which demonstrated that thyroid dysfunction was associated with longer PFS in patients with malignant melanoma (P=0.039) and other types of cancer (P=0.002), but not in those with lung cancer (P=0.083). These findings were noted in patients who received PD-1 inhibitor monotherapy (P=0.003), but not PD-1 inhibitor plus chemotherapy (P=0.172) or PD-1 inhibitor plus targeted therapy (P=0.582). Finally, thyroid dysfunction [P=0.001; hazard ratio (HR)=0.260] and PD-1 inhibitor monotherapy (P=0.015; HR=2.231) were identified as independent factors that could predict PFS. In conclusion, the present study demonstrated that thyroid dysfunction during PD-1 inhibitor treatment could be used as a potential marker for the prognosis of favorable PFS in patients with cancer.

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Section: Discussionsupporting

confidence: 91%

Thyroid dysfunction during PD‑1 inhibitor treatment in patients with cancer: Incidence and association with progression‑free survival

Wu¹,

Wang²,

Bai

et al. 2022

Oncol Lett

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“…A total of 57 studies included OS data ( 13 – 18 , 32 – 39 , 41 – 58 , 60 – 71 , 73 – 85 ) and 34 included PFS data ( 14 , 15 , 18 , 32 , 33 , 36 – 42 , 47 , 49 , 54 , 55 , 58 – 60 , 62 , 64 , 66 , 68 – 72 , 75 , 76 , 78 , 79 , 81 , 82 , 85 ). Geographically, 18 studies were from Asian countries ( 35 , 39 , 48 , 56 , 61 – 66 , 69 , 76 – 81 , 85 ), 24 from European countries ( 13 – 16 , 33 , 36 – 38 , 41 – 43 , 45 , 47 , 50 , 53 – 55 , 58 , 59 , 68 , 74 , 75 , 82 , 84 ), six from the United States ( 32 , 44 , 46 , 52 , 67 , 70 ...…”

Section: Resultsmentioning

confidence: 99%

“…A total of 57 articles assessed the association between the occurrence of irAEs and OS in patients with melanoma ( 13 – 18 , 32 – 39 , 41 – 58 , 60 – 71 , 73 – 75 , 77 – 86 ), and 34 assessed PFS ( 14 , 15 , 18 , 32 , 34 , 36 – 42 , 47 , 49 , 54 , 55 , 58 – 60 , 62 , 64 , 66 , 68 – 72 , 75 , 76 , 78 , 79 , 81 , 82 , 85 ). Among these, the study of Abu-Sbeih et al.…”

Section: Resultsmentioning

confidence: 99%

“…( 76 ) contained OS and PFS data of two different irAE grades; the studies of Frelau et al. ( 47 ) and Lang et al. ( 58 ) included OS and PFS data of two types of irAEs; Serna-Higuita et al.’s ( 68 ) study included OS data of two different irAE grades; and Dimitriou et al.’s ( 41 ) study included data of three different treatment cohorts.…”

Section: Resultsmentioning

confidence: 99%

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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

Sun

et al. 2022

Front. Oncol.

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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.

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“…Several studies demonstrated that the occurrence of TD is a promising pronostic factor in cancer patients receiving ICIs, including lung cancer [ 17 , 18 ] and melanoma [ 26 ]. However, no research has investigated the association of TD and prognosis of ESCC.…”

Section: Discussionmentioning

confidence: 99%

Thyroid Dysfunction as a Predictive Indicator in Camrelizumab of Advanced Esophageal Squamous Cell Carcinoma

Chen

Zhuang

Zhang

et al. 2022

Journal of Immunology Research

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Thyroid dysfunction (TD) induced by programmed death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) has been widely reported. However, the effects of ICI-induced TD on the survival of patients with esophageal squamous cell carcinoma (ESCC) have not been described. Herein, a retrospective study was conducted, which 82 patients with advanced metastatic or recurrent ESCC treated with camrelizumab were enrolled. Twenty patients (24.4%) experienced TD during camrelizumab treatment with or without chemotherapy. The median onset time of TD was 1.7 months. The incidence of TD was 35.6% in patients who previously received thoracic radiotherapy versus 10.8% in patients who did not (P =0.009). Patients with TD had significantly longer median progression-free survival (5.5 months vs 3.5 months, P =0.035) and overall survival (26.7 months vs 11.5 months, P <0.001). TD is frequently observed in ESCC patients treated with camrelizumab and especially in patients who received radiotherapy previously. ESCC patients with TD during ICIs treatment often have better prognosis.

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Prognostic impact of thyroid dysfunctions on progression-free survival in patients with metastatic melanoma treated with anti-PD-1 antibodies

Cited by 8 publications

References 44 publications

Thyroid dysfunction during PD‑1 inhibitor treatment in patients with cancer: Incidence and association with progression‑free survival

Thyroid dysfunction during PD‑1 inhibitor treatment in patients with cancer: Incidence and association with progression‑free survival

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

Thyroid Dysfunction as a Predictive Indicator in Camrelizumab of Advanced Esophageal Squamous Cell Carcinoma

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