Treatment (tx) with tyrosine kinase inhibitors (TKIs) for patients (pts) with differentiated thyroid cancer (DTC): The M. D. Anderson Cancer Center (MDACC) experience

Abstract

6060 Background: DTC is a relatively common tumor and about 20% will develop distant metastases (mets) of which at least 50% will not respond to standard tx. Until recently, tx for pts with progressive, RAI negative disease was limited. However, the identification of biologic targets in DTC has led to several trials with TKIs. Objectives: We sought to describe the MDACC experience with off-label use of TKIs to determine which pts benefit the most. Methods: Adult pts with a diagnosis of DTC treated with single agent sorafenib (SOR) or sunitinib (SUN), and who had a baseline and at least 1 follow-up (f/u) scan after 3 months (mos) of therapy, were included. All imaging data, as well as the TSH-suppressed thyroglobulin (TG) levels corresponding to each scan date were collected. RECIST was used to determine response. Results: We identified 33 pts from our clinical database. 15 pts met inclusion criteria: 9 women, 6 men. No pts were excluded due to progression or death before 3 mos. Median age 61 years (range, 38–83). 7 patients had papillary, 6 follicular (including 2 insular subtypes), 2 Hurthle cell. Most patients had RAI negative disease. SOR was used in 13, SUN in 2. Both SUN pts had been on SOR; 1 failed and 1 had intolerable side effects to SOR. Median time on tx was 42 weeks. All pts had evidence of PD prior to start of tx. Best response was 3 (20%) PR, 9 (60%) SD, 3 (20%) PD. Clinical benefit (PR+SD) = 80%. The SUN pt who was refractory to SOR had a 38% reduction in tumor size. The most noticeable activity occurred in lung (median change: -16%), whereas lymph nodes had PD or SD (median change: +3%). The 2 pts with pleural mets had PD. Four pts had bone mets: 2 had XRT and had SD in bone, while the other 2 did not have XRT and had PD in bone. At 12 mos PFS was 65% and OS was 85%. Median f/u time was 16 mos. All histologic types had similar responses. Log (TG) correlated with response (p = 0.0005). Conclusions: SOR and SUN are effective in pts with widely metastatic, progressive DTC, with most pts achieving SD or PR. The most noticeable responses occurred in the lungs in contrast with minimal changes in nodal mets, suggesting a tissue-specific response to tx. Log (TG) significantly correlated with response to tx and therefore may have value as a surrogate marker of response. [Table: see text]