Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitors (TKIs) are the preferred treatment option for patients with advanced/metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutations and ALK rearrangements respectively. TKIs can theoretically induce thyroid dysfunction via actions on many levels of the hypothalamic-pituitary-thyroid axis. However, there are no published studies on occurrence of thyroid dysfunction related to use of EGFR/ALK TKIs in lung cancer. The current study aimed to prospectively and comprehensively evaluate incidence of thyroid dysfunction in NSCLC patients treated with EGFR and ALK inhibitors.
This prospective observational study at a tertiary care referral hospital included histologically/cytologically proven advanced/metastatic NSCLC patients treated with EGFR and ALK inhibitors over a period of 15 months. Thyroid function tests (including anti-TPO antibody) were done at baseline and repeated every month for first three months and then every three monthly for 12 months.
Six different drugs (EGFR and ALK inhibitors) were used for treatment of 50 NSCLC patients enrolled. Of these, four drugs caused thyroid dysfunction (EGFR inhibitors erlotinib, gefitinib and ALK inhibitors ceritinib, crizotinib). Thyroid dysfunction typically occurred at 1 month following start of TKI treatment. Prevalence of thyroid dysfunction was 8%. Distribution of subclinical (not requiring treatment) and overt thyroid dysfunction (requiring specific treatment) was 4% each. All patients were asymptomatic. Both patients with overt thyroid dysfunction had hypothyroidism while subclinical dysfunction was equally distributed between hypo- and hyper- thyroidism. All patients who developed thyroid dysfunction derived expected clinical benefit and none required TKI dose interruption or stoppage.
NSCLC patients may need to be monitored for occurrence of thyroid dysfunction during treatment with EGFR and ALK TKIs.

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