Endocrine Abstracts

Objective: Immune checkpoint inhibitors (ICI) are used for treatment of non-small cell lung cancer (NSCLC) and are associated with immune-related adverse events (irAEs), especially thyroid dysfunction. Few studies found an association between thyroid dysfunction and response to Nivolumab in the NSCLC The objective of this retrospective cohort study was to investigate the association between the occurrence of thyroid dysfunction in patients treated with Nivolumab for a NSCLC and treatment efficacy and to assess whether this association is function of severity and type of thyroid dysfunction.

Materials and methods: This study was performed at a referral oncology center between July 20, 2015 to June 30, 2018. Inclusion criteria were patients with histologically confirmed stage IIIB/IV NSCLC and progressive disease who initiated anti-PD-1 blockade (Nivolumab). The exclusion criteria were: patients whose primary tumor was not from bronchopulmonary origin; patients with a history of thyroid disease; patients not having any thyroid monitoring before/ during Nivolumab treatment. Thyroid function (TSH ± fT4, fT3) was monitored and patients were classified according to thyroid dysfunction occurrence (TD(+) vs TD(−)) and according to severity (moderate thyroid dysfunction: TSH level between 0.1–0.4 or 4.0–10 mIU/l, and severe thyroid dysfunction: TSH ≤ 0.1 or ≥10 mUI/l) and subtypes (isolated hypothyroidism, isolated thyrotoxicosis or thyroiditis (thyrotoxicosis then hypothyroidism)).

The primary clinical endpoints were the overall survival (OS) and progression-free survival (PFS). The secondary clinical endpoints were the objective response rate (ORR), the disease control rate (DCR) and the duration of response.

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 (15.2-not reached) vs 8.1 months (3–20.4) in TD (−) group (P < 0.001). PFS was also longer (8.7 months (2–27.1) in TD (+) vs 1.7 months (1.6–3.6) in TD (−) group (P < 0.001). Treatment response was also higher in TD(+) group vs TD(−) group : ORR was of 47.5% vs 12.8% (P < 0.001), PRR was of 20% vs 7.4% (P = 0.04), DCR was of 70% vs 27.7% (P < 0.001). In Cox proportional hazards analysis, thyroid dysfunction remained an independent prognostic factor associated with OS/PFS. Severity and subtypes of thyroid dysfunction were not correlated with survival outcomes.

Conclusions: This study found a high prevalence of thyroid dysfunction under Nivolumab, which appears to be an independant prognostic factor regardless of thyroid dysfunction severity and subtypes.