1862PDImpact of lung metastasis on overall survival (OS) in the phase III SELECT study with lenvatinib (LEN) in patients (pts) with radioiodine refractory differentiated thyroid cancer (RR-DTC)

Abstract Background In the randomized phase III SELECT study, LEN demonstrated a significant prolongation of progression-free survival compared with placebo (PBO) in pts with RR-DTC. There was no significant difference in overall survival (OS) between LEN and PBO arms which was likely due to > 80% of pts on the PBO arm crossing over to open-label LEN treatment. This exploratory post hoc analysis investigated the impact of measurable lung metastasis on OS from the SELECT study. Methods The hazard ratio (HR) for OS (data cutoff, September 1, 2016) and the 95% CIs were estimated using the Cox proportional hazards model. The influence of various baseline characteristics on OS was analyzed using a multivariate analysis based on a Cox proportional hazards model. Subgroup analysis of OS was conducted based on maximum size of measurable lung metastasis (≥ 1 cm per RECIST 1.1) at baseline. Results In the overall population (392 pts), median OS of LEN (261 pts) and PBO (131 pts, with 115 pts crossed over to LEN) arms, were 40.3 months (M) and 34.5 M, respectively (hazard ratio [HR] 0.87, 95% CI 0.66 –1.15, P = 0.3170). In 306 pts with lung metastasis of ≥ 1.0 cm, significant prolongation of OS was observed with LEN (199 pts) compared with PBO (107 pts, with 95 pts crossed over to LEN) (HR 0.63, 95% CI 0.47–0.85, P = 0.0025). This was maintained after adjustment for baseline characteristics in the multivariate model. Similar trends of OS prolongation by LEN were observed in pts with lung metastasis of ≥ 1.5 cm, ≥ 2.0 cm, and 1.0–2.0 cm (Table). Conclusions In pts with lung metastasis of ≥ 1.0 cm, LEN significantly prolonged OS compared to pts treated by PBO including those crossed over to LEN. This post-hoc analysis suggests that RR-DTC pts with lung metastasis could be candidates for targeted therapy. Table:1862PD Overall survival by size of measurable lung metastasis at baselineLung LesionNumber of PtsMedian OS (M)HR95% CIP ValueLENPBOLENPBO≥1.0 cm19910744.733.10.630.47 – 0.850.0025≥1.5 cm1508444.122.30.630.45 – 0.890.0082≥2.0 cm945834.719.30.650.44 – 0.980.03831.0–2.0 cm1054949.238.60.630.40 – 0.990.0438*≥ 1 cm per RECIST 1.1 Clinical trial identification NCT01321554; Release date: December 30, 2016. Editorial acknowledgement Oxford PharmaGenesis, Newtown, PA, USA; Funded by Eisai Inc. Legal entity responsible for the study Eisai Inc. and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding Eisai Inc. and Merck Sharp & Dohme C