Poster Presentation COSA 2015 ASM

Efficacy and safety of lenvatinib for the treatment of patients with 131I-refractory differentiated thyroid cancer with and without prior VEGF-targeted therapy (#362)

Kate Newbold 1 , Rosella Elisei 2 , Matthew Hiram Taylor 3 , Monika Krzyzanowska 4 , Manisha H Shah 5 , Ana O Hoff 6 , Bruce Robinson 7 , Corina Dutcus 8 , James Song 9 , Brett Hughes 10 , Mouhammed Amir Habra 11
  1. The Royal Marsden NHS Foundation Trust, London, United Kingdom
  2. Dipartimento Di Medicina Clinica e Sperimentale, Universita di Pisa, Pisa, Italy
  3. Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA
  4. Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, USA
  5. Department of Internal Medicine, The Ohio State University Comprehensive Cancer Centre, Columbus, OH, USA
  6. Instituto do Cancer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo , São Paulo , Brazil
  7. Department of Medicine, Northern Clinical School, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia
  8. Oncology Product Creation Unit, Eisai Inc, Woodcliff Lake, NJ, USA
  9. Eisai Inc, Woodcliff Lake, NJ, USA
  10. Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
  11. Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas, MD Anderson Cancer Centre, Houston, Texas, USA

Aims: Lenvatinib (LEN), an oral multikinase inhibitor of VEGFR1–3, FGFR1–4, PDGFRα, RET, and KIT, significantly prolonged progression-free survival (PFS) vs placebo in the phase 3 SELECT trial of patients (pts) with 131I-refractory differentiated thyroid cancer (RR-DTC). Here we report the prespecified analysis of LEN-treated pts based on prior VEGF-targeted therapy exposure.

Methods: Pts with measurable RR-DTC and independent radiologic documentation of disease progression within 13 months were randomized 2:1 to LEN (24 mg/d; 28-d cycle) or placebo. Pts were stratified by age, region, and prior VEGF-targeted therapy (0 [VEGF-naive] or 1 [prior-VEGF]).

Results: 195/261 (75%) LEN-treated and 104/131 (79%) placebo-treated pts were naive to VEGF-targeted therapy. 93 Pts had received prior-VEGF therapy: sorafenib, 77%; sunitinib, 9%; pazopanib, 5%; other, 9%. LEN prolonged PFS vs placebo in both groups (VEGF-naive: HR 0.20; 95% CI 0.14–0.27; P<0.0001; prior-VEGF: HR 0.22; 95% CI 0.12–0.41; P<0.0001). Objective response rates (ORR) were similar between both groups (Table). VEGF-naive pts received more cycles of LEN than prior-VEGF pts (medians of 16 and 12.5 cycles, respectively), but had lower overall daily dose intensity (16.1 and 20.1 mg/d, respectively). The proportion of LEN-treated pts with at least 1 dose reduction was similar (VEGF naive: 87%; prior-VEGF: 82%), but VEGF-naive pts had an earlier median time to first dose reduction than pts with prior-VEGF (8.9 and 14.8 weeks, respectively). Most common LEN-emergent adverse events for VEGF-naive and prior-VEGF pts were, respectively: hypertension (72% and 62%), diarrhea (70% and 61%), decreased appetite (54% and 55%), decreased weight (52% and 49%), and nausea (45% and 52%).

Conclusions: In SELECT, LEN conferred comparable efficacy in pts with and without prior exposure to VEGF-targeted therapy, with similar safety profiles.