LBA-06 - INTEGRATE: A randomized phase II double-blind placebo-controlled study of regorafenib (REG) in refractory advanced oesophagogastric cancer (AOGC) -...

Date 04 July 2015
Event WorldGI 2015
Session Oral and LBA abstracts
Topics Anti-Cancer Agents & Biologic Therapy
Oesophageal Cancer
Gastric Cancer
Presenter J.R. Zalcberg
Citation Annals of Oncology (2015) 26 (suppl_4): 117-122. 10.1093/annonc/mdv262
Authors J.R. Zalcberg1, S.Y. Rha2, J. Lee3, D. Goldstein4, A. Strickland5, Y. Bang6, N. Pavlakis7, K.M. Sjoquist8, E. Tsobanis9, A.J. Martin10, Y. Kang11, C.J. O'Callaghan12, N.C. Tebbutt13, J.Y. Cho14, L.R. Lipton15, M.J. Burnell16, T. Alcindor17, J.W. Kim18, S. Yip19, J. Simes20
  • 1Peter MacCallum Cancer Centre, Melbourne/AU
  • 2Yonsei University College of Medicine, Seoul/
  • 3Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul/
  • 4Prince of Wales Hospital, Sydney/AU
  • 5Monash Medical Centre, East Bentleigh/AU
  • 6Seoul National University Hospital, Seoul/KR
  • 7The University of Sydney, Sydney/AU
  • 8St. George Hospital, Sydney/AU
  • 9NHMRC Clinical Trials Centre, Camperdown/AU
  • 10University of Sydney, Sydney/AU
  • 11University of Ulsan College of Medicine, Seoul/KR
  • 12NCIC Clinical Trials Group, Kingston/CA
  • 13Austin Health, Melbourne/AU
  • 14Yonsei University College of Medicine, Seoul/KR
  • 15Western Health, Melbourne/AU
  • 16Saint John Regional Hospital, Saint John/CA
  • 17McGill University Health Centre, Montreal/CA
  • 18Seoul National University Bundang Hospital, Seongnam/KR
  • 19Sydney Catalyst Translational Cancer Research Centre, Sydney/AU
  • 20NHMRC Clinical Trials Centre, Sydney/AU

Abstract

Introduction

REG is an oral multi-kinase inhibitor warranting evaluation in AOGC following failure of 1st- or 2nd-line chemotherapy (CT) where few options exist.

Methods

International (Australia & New Zealand (ANZ), Korea, Canada (NCIC CTG)) phase II RCT with 2:1 randomisation to 160mg REG or matched placebo (PBO) on days (D) 1-21 each 28 D cycle until disease progression (PD) or prohibitive adverse events. Primary endpoint: progression free survival (PFS). Final analysis used data to 31 Dec 14.

Results

152 patients (pts) enrolled (Nov 12 to Feb 14) yielding 147 pts evaluable for analysis (97 REG and 50 PBO). M:F (118:29); primary site: OGJ (56), stomach (85); lines of prior CT: 1 (62), 2 (85); ECOG PS 0 (62): 1 (85). Median (med.) treatment wks: 8 (REG) v 4 (PBO). Med. REG dose intensity: 150mg (130mg Korea and 160mg ANZ/Can). 27 PBO pts received REG following PD. REG Med. PFS 11.1 wks (95% CI: 7.7–13.3) v PBO 3.9 wks (3.7 - 4.0), HR 0.40, p < 0.0001. Med. REG OS 25 wks (95% CI: 18.9-29.6) v PBO 19.4 wks (95% CI: 14.9–22.7), HR 0.74, p = 0.11. Pre-specified analyses found REG effect greater in Korea than ANZ/Can (HR 0.12 v 0.61, p = 0.0009) but consistent across age, NLR, primary site, lines of CT, peritoneal metastases (mets) presence, number of met. sites, and VEGF-A (Table). Results comparable for ITT population (n = 152). REG was well tolerated, with expected spectrum of toxicities.

Key sub-groups PFS HR (95% CI) P value Interaction p Value
Korea (n = 54) 0.12 (0.06–0.27) <0.0001
ANZ/Canada (n = 93) 0.61 (0.39–0.97) 0.03 0.0009
Lines of prior therapy
1 (n = 62) 0.49 (0.28–0.86) 0.01 0.50
2 (n = 85) 0.32 (0.19–0.55) <0.001
Neutrophil-lymphocyte ratio (NLR)
<3 (n = 71) 0.41 (0.23–0.70) 0.0007 0.72
≥ 3 (n = 76) 0.37 (0.22–0.64) 0.0001
Plasma VEGF-A (pg/ml)
Low (≤ 0.14), (n = 82) 0.39 (0.24–0.65) 0.0001 0.72
High (> 0.14), (n = 62) 0.42 (0.23–0.78) 0.003