Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2019

Analysis of overall survival (OS) based on early tumour shrinkage in the phase 3 METEOR study of cabozantinib (cabo) versus everolimus (eve) in advanced renal cell carcinoma (RCC) (#354)

T H Tan 1 , I Duran 2 , P Maroto 3 , C Suarez 4 , D Castellano 5 , X García del Muro 6 , L Costa 7 , L Martin-Couce 8 , F Benzaghou 9 , S Thomas 10 , D W Markby 10 , T K Choueiri 11
  1. Department of Medical Oncology, Royal Adelaide Hospital, North Terrace, Adelaide, Australia
  2. Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain
  3. Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  4. Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
  5. Hospital Universitario, 12 De Octubre, Madrid, Spain
  6. Medical Oncology Department, Institut Catalá d'Oncologia, IDIBELL, L'Hospitalet de Llobregat, Spain
  7. Centro Hospitalar de Lisboa Norte, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Alameda da Universidade, 1649-035 Lisbon, Portugal
  8. Ipsen Pharma, Torre Realia-Pl. Europa, 41-43, Planta 7, 08908 L'Hospitalet de Llobregat, Barcelona, Spain
  9. Ipsen Innovation, 5 Avenue du Canada, Z.I. Courtaboeuf, F-91940 Les Ulis, France
  10. EXELIXIS, 1851 Harbor Bay Pkwy, Alameda, CA 94502, USA
  11. Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

Background: Retrospective studies have shown that early tumour shrinkage (eTS), based on target lesion reduction from baseline to first post-baseline scan, has predictive value for targeted therapies in RCC (Grunwald 2015; Grunwald 2016); here we evaluate its impact on OS in the METEOR study (NCT01865747).

Methods: 658 pts were randomized 1:1 to receive cabo (60 mg qd) or eve (10 mg qd). Target lesion size was assessed by independent radiology review using CT/MRI scans at baseline, every 8 wk for the first 12 mo and every 12 wk thereafter. Median OS was estimated for pts with ≥30% eTS, any eTS or no eTS at first post-baseline scan (week 8); data cutoff, 2 October 2016 (Motzer 2018).

Results: Median follow-up was 28 mo (IQR 25, 30). Median (range) time to objective response was 1.91 (1.6, 11.0) mo with cabo and 2.14 (1.9, 9.2) mo with eve, and corresponded to the time to the first post-baseline scan. A greater proportion of pts had ≥30% eTS with cabo (20%) than with eve (5%) and the rate of any eTS was higher in the cabo arm (73%) than with eve (47%). Median OS with cabo vs eve for pts with ≥30% eTS was not reached (NR; 95% CI, 23.7–NR) vs 10.2 mo (95% CI, 3.9–NE), respectively (stratified HR, 0.45; 95% CI, 0.21–0.95; p<0.05). Median OS with cabo vs eve for pts with any eTS was 23.7 (95% CI, 21.7–27.7) vs 17.3 mo (95% CI, 15.4–20.8), respectively; (stratified HR, 0.62; 95% CI, 0.48–0.80; p<0.05). OS was similar for cabo and eve for pts with no eTS.

Conclusions: Cabo demonstrated a higher rate and greater magnitude of eTS at first post-baseline scan compared with eve, and eTS was associated with prolonged OS in pts treated with cabo.