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Thyroid dysfunction induced by immune checkpoint inhibitors is associated with a better progression-free survival and overall survival in non-small cell lung cancer: an original cohort study

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Abstract

Background

The objective of this study was to investigate the association between the onset of TD and treatment efficacy in NSCLC patients who initiated anti-PD-1 blockade (Nivolumab®) and to assess the impact of TD severity and subtype on nivolumab efficacy.

Materials and methods

This study was performed at a referral oncology center between July 20, 2015 and June 30, 2018. Patients with histologically confirmed stage IIIB/IV NSCLC in progression after one or two lines of treatment and who initiated Nivolumab were included. Thyroid function (TSH ± fT4, fT3) was monitored and patients were classified according to TD status [TD(+) versus TD(−)], severity [moderate thyroid dysfunction: TSH level between 0.1 and 0.4 or 4.0 and 10 mIU/L and severe thyroid dysfunction: TSH ≤ 0.1 or ≥ 10mUI/L) and subtype (isolated hypothyroidism, isolated hyperthyroidism and hyperthyroidism then hypothyroidism)]. Clinical endpoints were overall survival (OS) and progression-free survival (PFS).

Results

Among 194 eligible patients, 134 patients (median age, 63 yo; 70.1% male) were included. Forty (29.9%) patients were classified in TD(+) and had a longer OS of 29.8 months (95% CI 18.8-NR) versus 8.1 months (95% CI 5.5–11.5) in TD(−) group (p < 0.001). PFS was also longer (8.7 months (95% CI 5.3–15.1) in TD(+) versus 1.7 months (95% CI 1.6–1.9) in TD(−) group (p < 0.001). In Cox proportional hazards analysis, TD remained an independent predictive factor of OS/PFS. Severity and subtype of TD were not correlated with OS/PFS.

Conclusions

This study suggested that TD induced by Nivolumab appears to be an independent predictive factor of survival, irrespective of TD severity and subtype.

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Availability of data and materials

The datasets analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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Authors and Affiliations

  1. Department of Endocrinology, University Hospital of Brest, Boulevard Tanguy Prigent, 29609, Brest Cedex, France

    Philippe Thuillier, Claire Joly, Geneviève Crouzeix, Véronique Kerlan & Nathalie Roudaut

  2. EA GETBO 3878, University Hospital of Brest, Brest Cedex, France

    Philippe Thuillier, Claire Joly, Geneviève Crouzeix, Véronique Kerlan & Nathalie Roudaut

  3. Inserm CIC 1412, University Hospital of Brest, Brest Cedex, France

    Zarrin Alavi

  4. Department of Oncology, University Hospital of Brest, Brest Cedex, France

    Renaud Descourt & Gilles Quere

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  1. Philippe Thuillier
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Contributions

VK, NR are the guarantor of the study. PT, CJ, NR designed the study. PT realized the analysis. PT, CJ, ZA drafted the manuscript. PT, CJ, NR, ZA did the interpretation of data. NR, ZA, GC, GQ, RD, VK revised the manuscript for intellectual content.

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Correspondence to Philippe Thuillier.

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Thuillier, P., Joly, C., Alavi, Z. et al. Thyroid dysfunction induced by immune checkpoint inhibitors is associated with a better progression-free survival and overall survival in non-small cell lung cancer: an original cohort study. Cancer Immunol Immunother 70, 2023–2033 (2021). https://doi.org/10.1007/s00262-020-02802-6

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