Session: THR 312-340-Endocrine Neoplasia: Tumorigenesis and Therapeutics
Poster Board THR-331
Methods: SELECT–a phase 3 double-blind study–randomized patients with RR-DTC to 24 mg/d of LEN or PBO until disease progression, unacceptable toxicity, or death. Key inclusion criteria included independently verified disease progression within 13 months, 0 or 1 prior VEGF-targeted therapy, and serum thyroid-stimulating-hormone (TSH) levels ≤5.5mIU/L. When tolerated, active TSH suppression (≤0.5 mIU/L) by concomitant levothyroxine treatment was added.
Results: 392 Patients were randomized (LEN=261; PBO=131). Median baseline TSH levels were LEN, 0.05 mIU/L; PBO, 0.04 mIU/L. All patients received concomitant levothyroxine. Patient TSH levels in the LEN arm were already elevated relative to baseline (median 0.10 mIU/L; range, 0–39.1) by the time of first assessment (cycle 1 day 15). TSH levels peaked at cycle 2 (median TSH 0.16 mIU/L; range 0–93.2), but steadily declined after cycle 4. At study end, the median TSH level for the LEN arm was 0.08 mIU/L (range 0–17.8). There were no consistent changes in TSH levels in the PBO arm. Patients receiving LEN had worst post-baseline TSH levels of ≤0.5 mIU/L (n=99; 37.9%), >0.5-2.0 mIU/L (n=53; 20.3%), >2.0-5.0 mIU/L (n=25; 9.6%), and >5.0 mIU/L (n=80; 30.7%). 5 Patients experienced LEN-related hyperthyroidism and 9 patients experienced LEN-related hypothyroidism; all were Grade 1–2 events. There were no substantial differences in rates of dose modifications, study drug withdrawals, treatment exposure, or LEN-related adverse events based on worst post-baseline TSH levels. Objective response rates based on worst post-baseline TSH levels were: ≤0.5 mIU/L, 65.7%, >0.5-2.0 mIU/L, 69.8%; >2.0-5.0 mIU/L, 48.0%, and >5.0mIU/L, 68.8%. There was also no significant difference in PFS between patients based on worst post-baseline TSH levels (adjusted log-rank P=0.747).
Conclusions: An increase in TSH levels was a frequent complication; its direct relationship to LEN therapy has not been established. In this analysis, there was no evidence of a relationship between the maximum worst post-baseline TSH level and LEN dosing, or increased toxicities. There was also no evidence that TSH levels affected tumor responses to LEN treatment. This may be indicative of properties intrinsic to LEN, or reflective of frequent adjustment of thyroid hormone dosing by the treating physician to maintain low TSH levels. Further analyses are warranted.
Disclosure: SIS: Consultant, Roche Pharmaceuticals, Consultant, Genzyme Corporation, Consultant, Eli Lilly & Company, Consultant, Novo Nordisk, Consultant, Veracyte, Inc., Consultant, Astra Zeneca, Research Funding, Pfizer, Inc., Consultant, Bayer, Inc., Consultant, Exelixis, Inc., Consultant, Eisai. MS: Consultant, Genzyme Corporation, Consultant, Eisai, Consultant, Bayer, Inc., Consultant, Astra Zeneca. MT: Advisory Group Member, Lecture Fees, Speaker, Bristol-Myers Squibb, Advisory Group Member, Merck & Co.. BGR: Advisory Group Member, Bayer, Inc., Advisory Group Member, Astra Zeneca. KN: payment of registartion fees and flight to attend European Thyroid Association Annual Meeting topresent work arising from this trial in September 2014 , Eisai. AGG: Consultant, Eisai. MHS: Clinical Researcher, Bayer, Inc., Consultant, Exelixis, Inc., Consultant, Eisai. MHT: Advisory Group Member, Eisai. NK: Consultant, Eisai. CED: Employee, Eisai. AT: Employee, Eisai. LW: Consultant, Novartis Pharmaceuticals, Consultant, Eisai.
*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting
See more of: Abstracts - Orals, Poster Previews, and Posters