Pavlakis Nick, Sjoquist Katrin M, Martin Andrew J, Tsobanis Eric, Yip Sonia, Kang Yoon-Koo, Bang Yung-Jue, Alcindor Thierry, O'Callaghan Christopher J, Burnell Margot J, Tebbutt Niall C, Rha Sun Young, Lee Jeeyun, Cho Jae-Yong, Lipton Lara R, Wong Mark, Strickland Andrew, Kim Jin Won, Zalcberg John R, Simes John, Goldstein David
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.
J Clin Oncol. 2016 Aug 10;34(23):2728-35. doi: 10.1200/JCO.2015.65.1901. Epub 2016 Jun 20.
We evaluated the activity of regorafenib, an oral multikinase inhibitor, in advanced gastric adenocarcinoma.
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.
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.
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.
我们评估了口服多激酶抑制剂瑞戈非尼在晚期胃腺癌中的活性。
我们开展了一项国际（澳大利亚和新西兰、韩国以及加拿大）随机II期试验，患者按2:1的比例随机分组，并根据既往晚期疾病化疗线数（一线或二线）及地区进行分层。符合条件的患者在每28天周期的第1至21天接受最佳支持治疗加口服瑞戈非尼160mg或匹配的安慰剂，直至疾病进展或出现难以耐受的不良事件。主要终点是无进展生存期（PFS）。最终分析纳入了截至2014年12月31日的数据。
2012年11月7日至2014年2月25日，共随机分配了152例患者，产生147例可评估患者（瑞戈非尼组，n = 97；安慰剂组，n = 50）。基线特征均衡。两组间的中位PFS有显著差异（瑞戈非尼组为2.6个月；95%CI，1.8至3.1；安慰剂组为0.9个月；95%CI，0.9至0.9；风险比[HR]，0.40；95%CI，0.28至0.59；P <.001）。在韩国的疗效大于澳大利亚、新西兰和加拿大的总和（HR，0.12对0.61；交互作用P <.001），但在年龄、中性粒细胞与淋巴细胞比值、原发部位、化疗线数、腹膜转移情况、转移部位数量以及血浆血管内皮生长因子A方面效果一致。观察到瑞戈非尼有生存优势趋势（中位生存期，5.8个月；95%CI，4.4至6.8对4.5个月；95%CI，3.4至5.2；HR，0.74；P = 0.147）。29例分配至安慰剂组的患者在疾病进展后接受了开放标签的瑞戈非尼治疗。瑞戈非尼的毒性与先前报道相似。
在这项II期试验中，瑞戈非尼可有效延长难治性晚期胃腺癌的PFS。发现了地区差异，但瑞戈非尼在两个地区组均有效。计划开展III期试验。
