The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer.
The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer.
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DOI：
10.1016/j.ejca.2017.10.009
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
RECOURSE Study Group
中科院分区：
文献类型：
--
作者：
Van Cutsem E;Mayer RJ;Laurent S;Winkler R;Grávalos C;Benavides M;Longo-Munoz F;Portales F;Ciardiello F;Siena S;Yamaguchi K;Muro K;Denda T;Tsuji Y;Makris L;Loehrer P;Lenz HJ;Ohtsu A;RECOURSE Study Group
在III期临床试验中，trifluridine/tipiracil （TAS-102）延长了转移性结直肠癌患者的总生存期（OS）和无进展生存期（PFS），并且具有可接受的毒性。本分析调查了曲氟定/替吡拉西在resource亚组中的疗效和安全性。在预先指定的亚组中，使用Cox比例风险模型评估主要终点和关键次要终点，包括地理分区域（美国[USA]、欧盟[EU]、日本）、年龄（<65岁、≥65岁）和v-Ki-ras2 Kirsten大鼠肉瘤2病毒癌基因同源物（KRAS）状态（野生型、突变型）。安全性和耐受性用描述性统计报告。入组800例患者：美国，n = 99；EU, n = 403；日本，n = 266。年龄≥65岁的患者和突变KRAS肿瘤患者分别占该次区域所有患者的44%和51%。最终OS分析（包括89%的事件，而初始分析为72%）证实了trifluridine/tipiracil相关的生存获益，风险比（HR）为0.69（95%可信区间[CI] 0.59-0.81; P = 0.0001）。三个地区的中位总生存期（美国：HR 0.56; 95% CI 0.34-0.94; P = 0.0277；欧盟：HR 0.62; 95% CI 0.48-0.80; P = 0.0002；日本：HR 0.75; 95% CI 0.57-1.00; P = 0.0470）： trifluridine/tipiracil组为6.5-7.8个月，安慰剂组为4.3-6.7个月。中位PFS为曲氟定/替吡拉西组为2.0-2.8个月，安慰剂组为1.7-1.8个月；所有地区的hr都倾向于使用三氟吡啶/替吡拉西。trifluridine/tipiracil在老年患者和突变KRAS肿瘤患者中也观察到类似的临床益处。在安全性和耐受性方面，各次区域之间没有明显差异。Trifluridine/tipiracil在所有亚组中均有效，与年龄、地理来源或KRAS状态无关。该试验已在ClinicalTrials.gov注册：NCT01607957。
In the phase III RECOURSE trial, trifluridine/tipiracil (TAS-102) extended overall survival (OS) and progression-free survival (PFS) with an acceptable toxicity profile in patients with metastatic colorectal cancer refractory or intolerant to standard therapies. The present analysis investigated the efficacy and safety of trifluridine/tipiracil in RECOURSE subgroups. Primary and key secondary end-points were evaluated using a Cox proportional hazards model in prespecified subgroups, including geographical subregion (United States of America [USA], European Union [EU], Japan), age (<65 years, ≥65 years) and v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homologue (KRAS) status (wild type, mutant). Safety and tolerability were reported with descriptive statistics. Eight-hundred patients were enrolled: USA, n = 99; EU, n = 403; Japan, n = 266. Patients aged ≥65 years and those with mutant KRAS tumours comprised 44% and 51% of all patients in the subregions, respectively. Final OS analysis (including 89% of events, compared with 72% in the initial analysis) confirmed the survival benefit associated with trifluridine/tipiracil, with a hazard ratio (HR) of 0.69 (95% confidence interval [CI] 0.59–0.81; P = 0.0001). Median OS in the three regions was 6.5–7.8 months in the trifluridine/tipiracil arm and 4.3–6.7 months in the placebo arm (USA: HR 0.56; 95% CI 0.34–0.94; P = 0.0277; EU: HR 0.62; 95% CI 0.48–0.80; P = 0.0002; Japan: HR 0.75; 95% CI 0.57–1.00; P = 0.0470). Median PFS was 2.0–2.8 months for trifluridine/tipiracil and 1.7–1.8 months for placebo; HRs favoured trifluridine/tipiracil in all regions. Similar clinical benefits of trifluridine/tipiracil were observed in elderly patients and in those with mutant KRAS tumours. There were no marked differences among subregions in terms of safety and tolerability. Trifluridine/tipiracil was effective in all subgroups, regardless of age, geographical origin or KRAS status. This trial is registered with ClinicalTrials.gov: NCT01607957.
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影响因子：
5.2
作者：
Sakamoto K;Yokogawa T;Ueno H;Oguchi K;Kazuno H;Ishida K;Tanaka N;Osada A;Yamada Y;Okabe H;Matsuo K
通讯作者：
Matsuo K
影响因子：
3
作者：
Bendell JC;Rosen LS;Mayer RJ;Goldman JW;Infante JR;Benedetti F;Lin D;Mizuguchi H;Zergebel C;Patel MR
通讯作者：
Patel MR
影响因子：
8.8
作者：
Andreyev HJ;Norman AR;Cunningham D;Oates J;Dix BR;Iacopetta BJ;Young J;Walsh T;Ward R;Hawkins N;Beranek M;Jandik P;Benamouzig R;Jullian E;Laurent-Puig P;Olschwang S;Muller O;Hoffmann I;Rabes HM;Zietz C;Troungos C;Valavanis C;Yuen ST;Ho JW;Croke CT;O'Donoghue DP;Giaretti W;Rapallo A;Russo A;Bazan V;Tanaka M;Omura K;Azuma T;Ohkusa T;Fujimori T;Ono Y;Pauly M;Faber C;Glaesener R;de Goeij AF;Arends JW;Andersen SN;Lövig T;Breivik J;Gaudernack G;Clausen OP;De Angelis PD;Meling GI;Rognum TO;Smith R;Goh HS;Font A;Rosell R;Sun XF;Zhang H;Benhattar J;Losi L;Lee JQ;Wang ST;Clarke PA;Bell S;Quirke P;Bubb VJ;Piris J;Cruickshank NR;Morton D;Fox JC;Al-Mulla F;Lees N;Hall CN;Snary D;Wilkinson K;Dillon D;Costa J;Pricolo VE;Finkelstein SD;Thebo JS;Senagore AJ;Halter SA;Wadler S;Malik S;Krtolica K;Urosevic N
通讯作者：
Urosevic N
影响因子：
8.8
作者：
Doi, T.;Ohtsu, A.;Sasaki, T.
通讯作者：
Sasaki, T.
影响因子：
3.4
作者：
Overman, Michael J.;Varadhachary, Gauri;Abbruzzese, James L.
通讯作者：
Abbruzzese, James L.