A randomized, double-blind, phase 2 study of ruxolitinib or placebo in combination with capecitabine in patients with advanced HER2-negative breast cancer and elevated C-reactive protein, a marker of systemic inflammation
A randomized, double-blind, phase 2 study of ruxolitinib or placebo in combination with capecitabine in patients with advanced HER2-negative breast cancer and elevated C-reactive protein, a marker of systemic inflammation
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DOI：
10.1007/s10549-018-4770-6
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发表时间：
2018-08-01
影响因子：
3.8
通讯作者：
Rugo, Hope S.
中科院分区：
文献类型：
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作者：
O'Shaughnessy, Joyce;DeMichele, Angela;Rugo, Hope S.
Janus相关激酶(JAK)/信号转导和转录激活因子通路是炎症信号的关键调节因子，与肿瘤的发生、细胞存活和进展有关。这项随机的第二阶段试验评估了在HER2阴性的晚期乳腺癌和高度全身炎症(改良格拉斯哥预后评分[MGPS]ae 1)患者中，加入JAK1/JAK2抑制剂ruxolitinib治疗卡培他滨的有效性和安全性。对于既往激素治疗的疾病进展的晚期或转移性疾病或激素受体阳性患者，使用ae 2化疗方案的患者被随机分为1：1至21天周期的ruxolitinib(n=76)或安慰剂(n=73)+capecitabine。主要终点是总存活率(OS)。基线特征在组间很好地平衡。鲁索利替尼+卡培他滨组与安慰剂组+卡培他滨组的中位OS分别为11.2个月和10.9个月(对数等级检验P=0.762)；中位无进展生存期分别为4.5月和2.5月(对数等级检验P=0.151)；总有效率分别为28.9%和13.7%(Cochran-Mantel-Haenszel检验P=0.024)。与安慰剂加卡培他滨相比，服用鲁索利替尼加卡培他滨的患者的健康相关生活质量(HRQOL)发生了更有利的变化。两种方案总体上都是可以耐受的。与安慰剂加卡培他滨相比，鲁索利替尼加卡培他滨的3/4级贫血发生率(25.4%比5.6%)更高，3/4级掌底红肿感觉的发生率(1.4%比12.7%)更低。对于晚期乳腺癌和高度全身炎症的患者，在卡培他滨的基础上加用鲁索利替尼是可以接受的；ORR数值更大，观察到更有利的HRQOL改变，但与安慰剂加卡培他滨相比，OS和PFS都没有改善。
The Janus-associated kinase (JAK)/signal transducer and activator of transcription pathway is a key regulator of inflammatory signaling, associated with tumorigenesis, cell survival, and progression. This randomized phase 2 trial evaluated the efficacy and safety of the addition of ruxolitinib, a JAK1/JAK2 inhibitor, to capecitabine in patients with HER2-negative advanced breast cancer and high systemic inflammation (modified Glasgow Prognostic Score [mGPS] ae 1).Patients with ae 2 prior chemotherapy regimens for advanced or metastatic disease or hormone receptor-positive patients with disease progression on prior hormonal therapies were randomized 1:1 to 21-day cycles of ruxolitinib (n = 76) or placebo (n = 73) plus capecitabine. The primary endpoint was overall survival (OS).Baseline characteristics were well balanced between groups. For ruxolitinib plus capecitabine versus placebo plus capecitabine, median OS was 11.2 months versus 10.9 months (log-rank test P = 0.762); median progression-free survival (PFS) was 4.5 months versus 2.5 months (log-rank test P = 0.151); and overall response rate (ORR) was 28.9% versus 13.7% (Cochran-Mantel-Haenszel test P = 0.024), respectively. A more favorable change in health-related quality of life (HRQoL) was observed with ruxolitinib plus capecitabine versus placebo plus capecitabine. Both regimens were generally tolerable. A higher incidence of grade 3/4 anemia (25.4% vs 5.6%) and a lower incidence of grade 3/4 palmar-plantar erythrodysesthesia (1.4% vs 12.7%) occurred with ruxolitinib plus capecitabine versus placebo plus capecitabine.The addition of ruxolitinib to capecitabine for patients with advanced breast cancer and high systemic inflammation was generally tolerable; ORR was numerically greater, a more favorable change in HRQoL was observed, but neither OS nor PFS was improved compared with placebo plus capecitabine.