Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies.
Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies.
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DOI：
10.1007/s10637-018-0580-2
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发表时间：
2018-08
影响因子：
3.4
通讯作者：
O'Reilly EM
中科院分区：
文献类型：
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作者：
Hurwitz H;Van Cutsem E;Bendell J;Hidalgo M;Li CP;Salvo MG;Macarulla T;Sahai V;Sama A;Greeno E;Yu KH;Verslype C;Dawkins F;Walker C;Clark J;O'Reilly EM
Ruxolitinib，Janus激酶1（JAK 1）/JAK 2抑制剂，联合卡培他滨在随机II期RECAP研究中对转移性胰腺癌和全身性炎症（C反应蛋白[CRP] >13 mg/dL）患者的亚组分析中与卡培他滨相比改善了总生存期（OS）。我们报告了两项随机III期研究的结果，JANUS 1（）和JANUS 2（）。患有晚期/转移性胰腺癌、既往接受过一种化疗方案且CRP >10 mg/L的成人患者按1：1（根据改良格拉斯哥预后评分[1 vs 2]和东部肿瘤协作组体能状态[0/1 vs 2]分层）随机分配至21天周期的鲁索替尼15 mg每日2次+卡培他滨2000 mg/m2/天（第1-14天）或安慰剂+卡培他滨。主要终点为OS。两项研究均在JANUS 1的计划中期无效/有效性分析后终止。总体而言，JANUS 1（ruxolitinib：n = 161;安慰剂：n = 160）和JANUS 2（ruxolitinib：n = 43;安慰剂：n = 43）分别有321例和86例患者接受随机分组。在JANUS 1中，治疗之间的OS或无进展生存期（PFS）无显著差异（OS：风险比[HR]，0.969，95%置信区间[CI]，0.747-1.256; PFS：HR，1.056; 95% CI，0.827-1.348）或JANUS 2（OS：HR，1.584; 95% CI，0.886-2.830; PFS：HR，1.166; 95% CI，0.687-1.978）。最常见的血液学不良事件是贫血。未发现鲁索利替尼或卡培他滨的新安全性信号。Ruxolitinib加卡培他滨在难治性胰腺癌患者中耐受性良好;这种组合并没有提高生存率。
Ruxolitinib, a Janus kinase 1 (JAK1)/JAK2 inhibitor, plus capecitabine improved overall survival (OS) vs capecitabine in a subgroup analysis of patients with metastatic pancreatic cancer and systemic inflammation (C-reactive protein [CRP] >13 mg/dL) in the randomized phase II RECAP study. We report results from two randomized phase III studies, JANUS 1 () and JANUS 2 (). Adults with advanced/metastatic pancreatic cancer, one prior chemotherapy regimen and CRP >10 mg/L were randomized 1:1 (stratified by modified Glasgow Prognostic Score [1 vs 2] and Eastern Cooperative Oncology Group performance status [0/1 vs 2]) to 21-day cycles of ruxolitinib 15 mg twice daily plus capecitabine 2000 mg/m2/day (Days 1–14) or placebo plus capecitabine. The primary endpoint was OS. Both studies were terminated following a planned interim futility/efficacy analysis of JANUS 1. Overall, 321 and 86 patients were randomized in JANUS 1 (ruxolitinib: n = 161; placebo: n = 160) and JANUS 2 (ruxolitinib: n = 43; placebo: n = 43). There was no significant difference in OS or progression-free survival (PFS) between treatments in JANUS 1 (OS: hazard ratio [HR], 0.969, 95% confidence interval [CI], 0.747–1.256; PFS: HR, 1.056; 95% CI, 0.827–1.348) or JANUS 2 (OS: HR, 1.584; 95% CI, 0.886–2.830; PFS: HR, 1.166; 95% CI, 0.687–1.978). The most common hematologic adverse event was anemia. No new safety signals with ruxolitinib or capecitabine were identified. Ruxolitinib plus capecitabine was well tolerated in refractory pancreatic cancer patients; this combination did not improve survival.
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影响因子：
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作者：
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影响因子：
2.8
作者：
Ostojic A;Vrhovac R;Verstovsek S
通讯作者：
Verstovsek S
影响因子：
3.7
作者：
Jamieson, Nigel B.;Denley, Simon M.;McMillan, Donald C.
通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1158/1541-7786.mcr-16-0337
发表时间：
2017-04
期刊：
Molecular cancer research : MCR
影响因子：
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作者：
Smigiel JM;Parameswaran N;Jackson MW
通讯作者：
Jackson MW