1819OTumor growth rate and lenvatinib efficacy in radioiodine-refractory differentiated thyroid cancer

Background: Patients (pts) with differentiated thyroid cancer (DTC) are a heterogeneous group. Tumor growth rate (TGR) is correlated with life expectancy. Lenvatinib (LEN) is approved for radioiodine-refractory DTC based on the phase 3 SELECT trial. Here we examine TGR and efficacy outcomes from SELECT. Methods: Per SELECT eligibility criteria, pts had independent radiologic evidence of progression within 13 months prior to randomization (prebaseline) to LEN or placebo (PBO). In this post hoc, exploratory analysis, pre-randomization TGR was assessed per pt as: (sum of target lesions at baseline – sum of target lesions at prebaseline) divided by sum of target lesions at prebaseline, and then divided by the interval of time between the 2 examinations (in mos). Pts were dichotomized: slow TGR (TGR ≤ median TGR of all SELECT pts) vs fast TGR (TGR > median). Subgroups were: baseline liver metastases (yes vs no), age (≤65 vs > 65 y), histology (papillary vs follicular), ECOG PS (0 vs ≥ 1), and baseline thyroid-stimulating hormone (TSH) (≤0.1 vs > 0.1 uIU/mL). Results: In a multivariate model, TGR of pts on LEN was significantly associated with baseline tumor size, and baseline liver, bone, and other metastases. When comparing treatment arms, LEN improved progression-free survival (PFS) vs PBO in both slow TGR (median 20.2 vs 3.7 mos; HR 0.19; 95% CI 0.12–0.32; P < 0.001) and fast TGR groups (median 14.8 vs 3.5 mos; HR 0.20; 95% CI 0.12–0.33; P < 0.001). PFS of LEN-treated pts was significantly longer in the slow vs fast TGR group (median 20.2 vs 14.8 mos; HR 0.62; 95% CI 0.41–0.94; P = 0.0232). Differences were also seen for PFS between slow and fast TGR groups in pts >65 years, pts with ECOG PS 0, and pts with baseline TSH >0.1 uIU/mL. When comparing treatment arms, overall survival (OS) trends favored LEN over PBO in both slow (medians not reached [NR]; HR 0.53; 95% CI 0.29–0.97) and fast TGR groups (LEN, NR vs PBO, 20.3 mos; HR 0.78; 95% CI 0.43–1.39); however, significance was not achieved in the fast TGR group. Among pts on LEN, OS was similar between slow and fast TGR groups (HR 0.77; 95% CI 0.46–1.29); no trends were seen in subgroup analyses. Conclusions: In SELECT, LEN conferred benefit over PBO for all pts regardless of TGR; however, PFS was significantly longer in pts with slower TGR. Clinical trial identification: NCT01321554. Editorial acknowledgement: Editorial support was provided by Oxford PharmaGenesis of Newtown, PA, USA, and was sponsored by Eisai Inc. Legal entity responsible for the study: Eisai Inc. Funding: Eisai Inc. Disclosure: S. Leboulleux: Honoraria: Sanofi Genzyme, Bayer; Consulting/advisory role: Sanofi Genzyme; Research funding (institutional support): Bayer, Novartis; Travel/accommodations/expenses: Sanofi Genzyme. E.K. Lee: Consulting/advisory role: Eisai. L. Bastholt: Consulting/advisory role: Merck, BMS, Roche, Eisai, Incyte, Novartis; Travel/accommodations expenses: Merck, BMS, Novartis. M. Tahara: Honoraria: Bayer, Bristol-Myers Squibb, Eisai, Merck Serono, Takeda; Consulting/ advisory role: Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Ono Pharmaceutical, Pfizer; Research funding (institutional support): AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, Merck Sharp & Dohme, NanoCarrier, Novartis, Ono Pharmaceutical, Pfizer. L.J. Wirth: Consulting/advisory role: Amgen, Blueprint Medicines, Eisai, Loxo, Merck; Research funding: AstraZeneca, Bayer, Eisai. S.I. Sherman: Grant: Eisai, Pfizer, Genzyme; Personal fees: Eisai, Exelixis, Bayer, Onyx, AstraZeneca, Veracyte, NovoNordisk, Eli Lilly, Genzyme, Roche. B.G. Robinson: Personal fees: Eisai, AstraZeneca, Bayer. A. Teng, P. Joshi, S. Misir, C.E. Dutcus: Employee: Eisai Inc. R.M. Tuttle: Honoraria: Bayer, Eisai, Genzyme, Novo Nordisk; Consulting/advisory role: Eisai, Novo Nordisk; Research funding: AstraZeneca; Travel, accommodations, expenses: Bayer, Eisai, Genzyme, Novo Nordisk. M.J. Schlumberger: Consulting/advisory role: Bayer, Eisai, Ipsen, Sanofi Genzyme; Research funding: Eisai.