OR17-06 Efficacy of Lenvatinib in Patients with Radioiodine-Refractory Thyroid Cancer who Progressed on Sorafenib

Abstract Disclosure: F. Abothenain: None. A. Hadadi: None. L. Alobaid: None. A. Hakami: None. N. Ewain: None. D. Alturki: None. L. Yaseen: None. S. Abid: None. J. Mohammad: None. F. Sohail: None. A.S. Alzahrani: None. Introduction: The tyrosine kinase inhibitors (TKIS) Sorafenib and Lenvatinib are approved for progressive radioactive iodine refractory follicular cell-derived thyroid cancer (RAIR-TC). Development of resistance to these drugs is almost inevitable. In practice, it is common to shift from one of these drugs to another when resistance develops for either of them. However, the efficacy of the second TKI in such situations has not been well studied. In this report, we describe the efficacy of lenvatinib as a second TKi in a cohort of 19 pts (pts) with RAIR-TC who developed resistance to Sorafenib. Patients and Methods: We reviewed our pts who were treated with TKIs over about 10 years (November 2014-May 2023). Of 86 pts who received different types of TKIs, 19 were treated with sorafenib, developed resistance and shifted to lenvatinib. These included 8 (42%) males and 11 (58%) females, median age at the time of starting sorafenib was 53 years (range 41-79). They were all naïve to TKIs therapy. The original tumor subtypes were conventional PTC in 5 pts, follicular variant PTC in 2 pts, tall cell PTC in 4 pts, columnar cell subtype 2 pts, follicular thyroid cancer 2 pts and diffuse sclorosing subtype 1, hobnail PTC 1 pt, poorly differentiated TC in 1 pt and oncocytic subtype in 1 pts. The disease was inoperable locally invasive in 1 pt, with distant metastases at the time of diagnosis in 14 pts, and locally invasive with distant metastases in 4 pts. For initial management, 9 pts had thyroidectomy and I-131, 9 pts had thyroidectomy, I-131 and XRT and 1 had thyroidectomy and XRT. I-131 was given 30 times to the 19 pts (median cumulative dose 207 mCi, range 97-757). XRT was administered to 10 pts (median 5000 cGy, range 2000-6200). The median time from the initial surgery until using TKI was 70 months (range 6-192) and the median time on Sorafenib was 26.5 months (range 12-72). The response to TKIs was evaluated using the modified RECIST criteria. Results: The response achieved by sorafenib before progression was stable disease in 11 pts (57.9%), partial response in 2 pts (10.5%), and progressive disease in 6 pts (31.6%). The indication for lenvatinib was progression on sorafenib in all the 19 pts and the outcome of lenvatinib therapy was stable disease in 3 pts (15.8%), partial response in 3 pts (15.8%), progressive disease in 2 pts (10.5%), death due to TC in 9 pts (47%), death due to other causes in 2 pts (10.%%). The median duration of follow-up since the initial diagnosis of TC was 141 months (37-300) and the median duration on TKIs (1 and 2) was 60 months (10-120). In both therapies, the usual side effects of TKIs were common but no pt needed to discontinue therapy. Conclusion: In pts with RAIR-TC who develop resistance to Sorafenib, Lenvatinib has an overall response rate of about 32% (1/3 of pts). Progression and death are common in this high-risk group occurring in about 60% of pts over a median period of about 5 years after the initiation of TKIs. Presentation: Sunday, July 13, 2025