B-TREUH: A single-arm phase II pilot study of euthyroid hypothyroxinemia in metastatic breast carcinoma.

Abstract

TPS1115 Background: It is estimated that there are approximately 155,000 people living with metastatic breast cancer in the US. Studies exploring the connection between hypothyroidism or hyperthyroidism and breast cancer have yielded varying results with up to 33% prevalence of thyroid disease in these patients. L-thyroxine (T4) is the most commonly prescribed agent in the US to manage hypothyroidism. However, there are data suggesting that T4 is a pro-oncogenic agent with proposed mechanisms such as stimulation of mitogenesis, angiogenesis, resistance to apoptosis. In addition, T4 May counter anti-PDL-1 and radiation effects. Triiodothyronine (T3), which is deiodinated form of T4 and also commercially available, is felt to be less oncogenic and less mitogenic. Therefore, exogenous supplementation of T3 would decrease the T4 levels creating the desired state of EUTHYROID HYPOTHYROXINEMIA. The study hypothesizes that replacing L-thyroxine (T4) with Triiodothyronine (T3) in hypothyroid patients with metastatic breast carcinoma, while they simultaneously continue to receive standard systemic therapy, with titrating T3 dose to achieve a state of Euthyroid Hypothyroxinemia would result in improved disease outcomes. Methods: Eligible participants are adults with metastatic breast carcinoma with estimated life expectancy of > 3months, hypothyroidism, and with normal TSH on L-thyroxine (T4). Following consent, participants will discontinue L-thyroixne (T4) and initiate Triiodothyronine (T3) dose based on current T4 dose after an appropriate washout period. Drug titration will be in accordance with thyroid function testing to maintain levels of free T4 at < 50% normal range. The treatment period will continue for 9 months with periodic assessment of disease status, quality of life (FACT-B) and laboratory measures. The primary endpoint is the progression free survival at 12 months while the secondary endpoints are prevalence of hypothyroidism in the cohort, overall survival, quality of life, and duration of time to achieve the Euthyroid Hypothyroxinemia state. Given many uncertainties to calculate power precisely, the sample size is estimated to be approximately 30 patients. Clinical trial information: NCT03787303 .