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J Clin Oncol. 2016 Aug 10;34(23):2728-35. doi: 10.1200/JCO.2015.65.1901. Epub 2016 Jun 20.

Regorafenib for the Treatment of Advanced Gastric Cancer (INTEGRATE): A Multinational Placebo-Controlled Phase II Trial.

Author information

1
Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada. nick.pavlakis@sydney.edu.au.
2
Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada.

Abstract

PURPOSE:

We evaluated the activity of regorafenib, an oral multikinase inhibitor, in advanced gastric adenocarcinoma.

PATIENTS AND METHODS:

We conducted an international (Australia and New Zealand, South Korea, and Canada) randomized phase II trial in which patients were randomly assigned at a two-to-one ratio and stratified by lines of prior chemotherapy for advanced disease (one v two) and region. Eligible patients received best supportive care plus regorafenib 160 mg or matching placebo orally on days 1 to 21 of each 28-day cycle until disease progression or prohibitive adverse events occurred. The primary end point was progression-free survival (PFS). Final analysis included data to December 31, 2014.

RESULTS:

A total of 152 patients were randomly assigned from November 7, 2012, to February 25, 2014, yielding 147 evaluable patients (regorafenib, n = 97; placebo, n = 50). Baseline characteristics were balanced. Median PFS significantly differed between groups (regorafenib, 2.6 months; 95% CI, 1.8 to 3.1 and placebo, 0.9 months; 95% CI, 0.9 to 0.9; hazard ratio [HR], 0.40; 95% CI, 0.28 to 0.59; P < .001). The effect was greater in South Korea than in Australia, New Zealand, and Canada combined (HR, 0.12 v 0.61; interaction P < .001) but consistent across age, neutrophil-to-lymphocyte ratio, primary site, lines of chemotherapy, peritoneal metastasis presence, number of metastatic sites, and plasma vascular endothelial growth factor A. A survival trend in favor of regorafenib was seen (median, 5.8 months; 95% CI, 4.4 to 6.8 v 4.5 months; 95% CI, 3.4 to 5.2; HR, 0.74; P = .147). Twenty-nine patients assigned to placebo received open-label regorafenib after disease progression. Regorafenib toxicity was similar to that previously reported.

CONCLUSION:

In this phase II trial, regorafenib was effective in prolonging PFS in refractory advanced gastric adenocarcinoma. Regional differences were found, but regorafenib was effective in both regional groups. A phase III trial is planned.

PMID:
27325864
PMCID:
PMC5019744
DOI:
10.1200/JCO.2015.65.1901
[Indexed for MEDLINE]
Free PMC Article

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