Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, USA.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Breast Cancer Res Treat. 2018 Aug;170(3):547-557. doi: 10.1007/s10549-018-4770-6. Epub 2018 Apr 19.
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] ≥ 1).
Patients with ≤ 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.
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，与肿瘤发生、细胞存活和进展有关。这项随机的 2 期临床试验评估了 JAK1/JAK2 抑制剂芦可替尼联合卡培他滨治疗 HER2 阴性晚期乳腺癌和全身炎症较高（改良格拉斯哥预后评分[mgPS]≥1）患者的疗效和安全性。
患者有≤2 种晚期或转移性疾病的化疗方案，或激素受体阳性患者在先前的激素治疗中疾病进展，随机 1:1 接受 21 天周期的芦可替尼（n=76）或安慰剂（n=73）联合卡培他滨。主要终点是总生存期（OS）。
两组患者的基线特征平衡良好。与安慰剂加卡培他滨相比，芦可替尼加卡培他滨的中位 OS 为 11.2 个月对 10.9 个月（对数秩检验 P=0.762）；中位无进展生存期（PFS）为 4.5 个月对 2.5 个月（对数秩检验 P=0.151）；总缓解率（ORR）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，芦可替尼加卡培他滨可观察到更有利的健康相关生活质量（HRQoL）变化。两种方案均具有良好的耐受性。芦可替尼加卡培他滨组的 3/4 级贫血发生率较高（25.4%比 5.6%），3/4 级手掌-足底红细胞感觉异常发生率较低（1.4%比 12.7%）。
芦可替尼联合卡培他滨治疗晚期乳腺癌和全身炎症较高的患者耐受性良好；ORR 较高，HRQoL 改善更明显，但与安慰剂加卡培他滨相比，OS 和 PFS 无改善。
