局部和全身炎症反应（INFL）是癌症（包括胰腺癌）的特点，会造成不利影响预后。鉴于JAK-STAT信号传导在癌症局部和全身炎症反应的作用，研究人员针对初始治疗耐受的转移性胰腺癌患者，考虑ruxolitinib（RUX，一种JAK1/JAK2抑制剂）的疗效和安全性，联合卡培他滨作为二线治疗方案进行了研究。下面和大家提前分享这项研究。

研究详情：

接受吉西他滨治疗后进展，有充分的体能状态和器官功能的患者都纳入该项试验。RUX+CAPE在9个安全性患者组中耐受性良好。随后，127例患者被随机分配到CAPE 1000mg/m² BID第1～14天，联合RUX 15mg BID或者安慰剂在一个21天周期的第1～21天。主要终点是0S；次要终点是包括PFS和ORR。为了检测满足双侧α=0.2和β＜0.2的HR≤0.6，最终分析计划发生在97例死亡后。亚组分析被预先规定，来探索治疗的异质性，和关于RUX将会优先使伴有INFL证据的患者获益的假说。

研究结果：

在随机人群中，OS和PFS支持RUX（表）。RUX组已证实的ORR为7.8%，PBO组为0%。INFL患者亚组中，通过血清C反应蛋白测定（CRP＞13mg/L中位数），OS明显支持RUX超过PBO（表）。在这一亚组中，RUX组3个月和6个月的存活率为48%和42% vs PBO组的29%和11%。CRP≥13mg/L的患者中，OS和PFS的显著获益没有观察到（HR=0.89和0.82）。通过改良的Glasgow Prognostic评分（mGPS，一种癌症INFL衡量措施）归类的患者可以观察到OS获益（mGPS 0，1，2的HRs分别为0.91，0.71，0.49）。

表

RUX和CAPE的联合方案一般耐受性良好。3或者4级（G3/4）不良反应发生率RUX组为75%，PBO组为82%。G3/4中性粒细胞减少和血小板减少症在RUX组患者中不常见（分别为1.7%和0%）。RUX组（15.3%）患者发生G3/4贫血比PBO组（1.7%）率高。

研究结论：

Ruxolitinib可以提高以CRP升高或者mGPS评分1或2为特征的转移性胰腺癌患者的总生存期和无进展生存期。临床试验信息：NCT01423604。

医脉通整理报道，转载请注明出处。

会议专题》》》2014年ASCO年会专题报道

阅读摘要原文

A randomized double-blind phase 2 study of ruxolitinib (RUX) or placebo (PBO) with capecitabine (CAPE) as second-line therapy in patients (pts) with metastatic pancreatic cancer (mPC).（Abstract4000）

Authors: Herbert Hurwitz, Nikhil Uppal, Stephanie Ann Wagner, et al.

Session Type: Oral Abstract Session

Background: Local and systemic inflammation (INFL) are hallmarks of cancer, including PC, that adversely impact prognosis. Given the role of JAK-STAT signaling in cancer INFL, the efficacy and safety of RUX, a JAK1/JAK2 inhibitor, given with CAPE in pts with mPC refractory to initial therapy was explored.

Methods: Pts with adequate performance status and organ function who progressed after gemcitabine treatment were included. RUX + CAPE was well tolerated in a 9 pt safety run-in. Subsequently, 127 pts were randomized to CAPE 1000 mg/m2 BID days 1–14 with either RUX 15 mg BID or PBO on days 1–21 of a 21-day cycle. The primary endpoint was OS; secondary endpoints included PFS and ORR. To detect a HR ≤0.6 with 2-sided α=0.2 and β<0.2, final analysis was planned to occur after 97 deaths. Subgroup analyses were prespecified to explore treatment heterogeneity and a hypothesis that RUX would preferentially benefit pts with evidence of INFL.

Results: In the randomized population, OS and PFS favored RUX (Table). Confirmed ORR was 7.8% for RUX and 0% for PBO. In a prespecified subgroup of pts with INFL, as measured by serum C-reactive protein (CRP > group median of 13 mg/L), OS significantly favored RUX over PBO (Table). In this subgroup, 3 and 6 month survival was 48% and 42% with RUX vs 29% and 11% with PBO, respectively. In pts with CRP ≤13 mg/L, significant benefits in OS or PFS were not observed (HR = 0.89 and 0.82, respectively). OS benefit was also seen in pts classified by modified Glasgow Prognostic Score (mGPS), a measure of INFL in cancer (HRs 0.91, 0.71, 0.49 for mGPS 0, 1, 2, respectively). The combination of RUX and CAPE was generally well tolerated. Grade 3 or 4 (G3/4) adverse events occurred in 75% and 82% of RUX and PBO pts, respectively. G3/4 neutropenia and thrombocytopenia were uncommon in RUX pts (1.7% and 0%, respectively). G3/4 anemia occurred more frequently on RUX (15.3%) than PBO (1.7%).

Conclusions: RUX may improve OS and PFS in mPC pts with INFL characterized by elevated CRP or mGPS of 1 or 2. Clinical trial information: NCT01423604.