Poster Presentation COSA 2015 ASM

Effect of age and lenvatinib treatment on overall survival for patients with 131I-refractory differentiated thyroid cancer in SELECT (#363)

Marcia Brose 1 , Martin Schlumberger 2 , Makoto Tahara 3 , Lori Wirth 4 , Bruce Robinson 5 , Rossella Elisei 6 , Kate Newbold 7 , Naomi Kiyota 8 , Ana O Hoff 9 , Corina Dutcus 10 , James Song 11 , Brett Hughes 12 , Steven Sherman 13 , Matthew Hiram Taylor 14
  1. Department of Otorhinolaryngology: Head and Neck Surgery, Abramsom Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA
  2. Department of Nuclear Medicine and Endocrine Oncology, Centre de Reference Tumeurs Refractaires de la Thyroide, Gustave Roussy and University Paris-Sud, Villejuif, France
  3. Division of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan
  4. Department of Medicine, Harvard Medical School, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
  5. Department of Medicine, Northern Clinical School, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia
  6. Dipartimento Di Medicina Clinica e Sperimentale, Universita di Pisa, Pisa, Italy
  7. The Royal Marsden NHS Foundation Trust, London, United Kingdom
  8. Department of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Japan
  9. Instituto do Cancer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo , São Paulo , Brazil
  10. Oncology Product Creation Unit, Eisai Inc, Woodcliff Lake, NJ, USA
  11. Eisai Inc, Woodcliff Lake, NJ, USA
  12. Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
  13. Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
  14. Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA

Aims: The lenvatinib progression-free survival (PFS) benefit vs placebo in the phase 3 SELECT trial of radioiodine-refractory differentiated thyroid cancer (RR-DTC) was maintained in younger ( ≤65, median 56 years) and older ( >65, median 71 years) patients. Median overall survival (OS) was not reached at data cutoff, and OS was not significantly different between lenvatinib and placebo (HR 0.73; 95% CI 0.50-1.07; P=0.103). Here we examine the effect of age on OS in SELECT.

Methods: Patients with independently verified progressive RR-DTC were stratified by region, prior VEGF-targeted therapy, and age (younger: lenvatinib, n=155; placebo, n=81 vs older: lenvatinib, n=106; placebo, n=50) and randomized 2:1 to lenvatinib or placebo. Median follow-up was 17.1 months at data cutoff; 83% of placebo-treated patients crossed over to lenvatinib following disease progression.

Results: Median OS was only reached in older placebo-treated patients (18.4 months; 95% CI, 13.3-20.3). A significant difference in OS was observed in older patients, favoring lenvatinib (HR 0.53; 95% CI 0.31-0.91; P=0.020). There was no difference in OS between older and younger lenvatinib-treated patients (HR 0.78; 95% CI 0.49-1.26; P=0.304), but there was a statistically significant difference in the placebo arm, favoring younger patients (HR 0.48; 95% CI 0.27-0.85; P=0.010). We found no statistically significant differences between the age groups to explain this difference for the following factors: baseline ECOG (lenvatinib, P=0.56; placebo, P=0.46), prior VEGF-targeted therapy (lenvatinib, P=0.270, placebo, P=0.757), patients who crossed over to lenvatinib (P=0.441), or post-SELECT anticancer therapy (lenvatinib, P=0.567, placebo, P=0.112). Older patients had a nonsignificant, larger baseline median sum of target lesions (older: 64.9 mm; younger: 58.3 mm; P=0.113).

Conclusions: Older placebo-treated patients with RR-DTC had worse OS than younger placebo-treated patients in SELECT. This effect of age was completely mitigated by lenvatinib resulting in improved OS for patients >65 years treated with lenvatinib.