ECE2022 Rapid Communications Rapid Communications 3: Thyroid 1 (7 abstracts)
Immune-related thyroid dysfunctions during PD-1/PD-L1 inhibitors and their association to the oncological outcome: new evidence
Matteo Ferrari 1 , Alice Anna Nervo 1 , Sara Basile 1 , Enrica Migliore 2 , Valentina D’Angelo 1 , Giovanni Gruosso 1 , Daniela Rosso 1 , Francesca Retta 1 , Alessandro Piovesan 1 & Emanuela Arvat 1
1Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Oncological Endocrinology Unit, Torino, Italy; 2Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Cancer Epidemiology Unit, Torino, Italy
Background: Immune checkpoint inhibitors (ICIs) showed impressive results in several malignancies; however, a large spectrum of immune-related adverse events (IRAEs) may occur, including thyroid dysfunction (DYSTHYR). IRAEs seem to be associated with better cancer outcome; limited data suggested that thyroid toxicity could be a predictor of response to ICIs.
Patients and methods: We retrospectively evaluated all patients who started treatment with the programmed cell death protein-1 (PD-1) and its ligand (PD-L1) inhibitors between 2017 and 2020 at the Città della Salute e della Scienza Hospital (Department of Oncology). Patients with central hypothyroidism were excluded from the analysis. Both the new onset and the worsening of pre-existing DYSTHYR were recorded; hypothyroidism was categorized as grade (G) 1 or 2 according to TSH levels (< or ≥ 10 mU/l) similarly to thyrotoxicosis (G1 or 2 in case of TSH > or ≤ 0.1 mU/l). Radiological tumor response was defined according to RECIST criteria. Progression free survival (PFS) and overall survival (OS) were assessed and compared among different groups.
Results: Among 324 patients (median age 67 years, 70.7% males, 95.4% treated with anti-PD-1, 49.4% affected by lung cancer), DYSTHYR was observed in the 24.7% of the population, after a median time of 3.3 (1.8-6.2) months. The most recorded event was hypothyroidism (85%); DHYSTHYR was G2 in 70% of cases. No statistically significant benefit in terms of PFS was observed in patients with DYSTHYR. However, the development of DISTHYR was associated with a significantly longer OS (87.3% vs 73.5% at 12 months, P=0.03) and lower mortality (HR 0.61; 95% CI 0.39-0.95). Considering only patients without pre-existing thyroid dysfunction at baseline (277, 85.5% of the sample), a better OS was observed in case of DYSTHYR G2 in comparison to cases with DYSTHYR G1 or without DYSTHYR (P=0.03), with a decreased risk of death (HR 0.47; 95% CI 0.24-0.91).
Conclusions: DYSTHYR is a common IRAE during anti PD-1/PD-L1 treatment. We detected a better clinical outcome in patients with DISTHYR during ICIs, in terms of improved OS and reduced mortality. In subjects without pre-existing thyroid alteration, the benefit was observed especially in case of detection of higher TSH levels during ICIs.
Volume 81
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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