Results of a retrospective study suggested that an elevation in thyroid-stimulating hormone (TSH) level at 2 weeks was a potential indicator of response to first-line sunitinib in patients with metastatic renal cell carcinoma (mRCC). The findings of this study were published in BMC Cancer.

The development of new-onset hypothyroidism in patients with normal baseline biochemical indicators of thyroid function is well known as a potential adverse effect of treatment with sunitinib, a multitargeted receptor tyrosine kinase inhibitor, in the setting of metastatic RCC. In addition, a number of studies have demonstrated that the development of hypothyroidism in patients with metastatic RCC treated with sunitinib was associated with improved clinical outcomes, such as longer progression-free survival (PFS) and/or overall survival (OS).

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This focus of this retrospective study was the effect of early vs later increases in the level of thyroid-stimulating hormone (TSH) on clinical outcomes in 70 adult patients (aged 25 to 79 years; median age of 62 years) with metastatic clear cell RCC receiving first-line treatment with sunitinib. Median follow-up was 19.2 months.

Levels of TSH were assessed at baseline and on day 15 as well as at the start and end of each treatment cycle (days 1 and 28) thereafter.

Of the 62 patients evaluable for response, 42.9% had a TSH level above the upper limit of normal by day 15, which increased to 50% of patients by day 75. Median TSH levels increased from 1.96 mU/L (baseline), to 3.88 mU/L (day 15), to 5.19 mU/L (day 75).

Interestingly, those patients experiencing an objective response (OR), stable disease (SD), or progressive disease (PD) had a ratio of day-15 TSH to baseline TSH of 3.33, 2.18, and 1.59, respectively. However, these response differences were less marked for those patient with elevated TSH levels at day 75, with day-75 to baseline ratios of 3.96, 3.41, and 3.29 in those achieving an OR, an SD, or PD, respectively.

“A highly significant observation in our study is that the magnitude of TSH increase in the very early stages of treatment with sunitinib (day-15) appears to have a prognostic value,” the study authors commented.

Other findings of the study were a median PFS of 11.92 months versus 8.63 months for patients with a day-15 TSH to baseline TSH ratio of more than 2 and less than 2 (hazard [HR], 1.76; 95% CI, 1.033-3.288; P [log rank] =.0476). This finding was also reflected in OS, with median OS of 3.10 years versus 1.08 years for those with a day-15 TSH to baseline TSH ratio of more than 2 and less than 2 (HR, 1.73; 95% CI, 1.556-5.394; P [log rank] =.0011).


Vasileiadis T, Chrisofos M, Safioleas M, et al.  Ιmpact of sunitinib-induced hypothyroidism on survival of patients with metastatic renal cancer. BMC Cancer. 2019; 19:407.