Phase II study of single-agent bosutinib, a Src/Abl tyrosine kinase inhibitor, in patients with locally advanced or metastatic breast cancer pretreated with chemotherapy
Phase II study of single-agent bosutinib, a Src/Abl tyrosine kinase inhibitor, in patients with locally advanced or metastatic breast cancer pretreated with chemotherapy
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DOI：
10.1093/annonc/mdr261
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发表时间：
2012-03-01
影响因子：
50.5
通讯作者：
Epstein, R. J.
中科院分区：
文献类型：
--
作者：
Campone, M.;Bondarenko, I.;Epstein, R. J.
背景：这项II期研究评估了单药博舒替尼在预先治疗的局部晚期或转移性乳腺癌患者中的作用。患者和方法：患者口服博舒替尼400mg /d。主要终点是16周时的无进展生存（PFS）率。次要终点包括客观缓解率、临床获益率、2年总生存率、安全性和骨吸收/形成生物标志物水平的变化。结果：73例患者入组并接受治疗。从诊断转移性疾病到开始博舒替尼治疗的中位时间为24.5个月。对于意向治疗人群，16周时的PFS率为39.6%。出乎意料的是，所有应答的患者（n = 4）均为激素受体阳性。临床获益率为27.4%。2年总生存率为26.4%。主要毒性反应为腹泻（66%）、恶心（55%）和呕吐（47%）。14例（19%）患者出现3-4级实验室转氨酶升高。骨髓抑制最小。未观察到骨吸收/形成生物标志物水平的一致变化。结论：博舒替尼在延长局部晚期或转移性乳腺癌化疗前患者的进展时间方面显示出良好的疗效。博舒替尼总体耐受性良好，在类似的患者群体中，其安全性与Src/Abl酪氨酸激酶抑制剂达沙替尼不同。
Background: This phase II study evaluated single-agent bosutinib in pretreated patients with locally advanced or metastatic breast cancer.Patients and methods: Patients received oral bosutinib 400 mg/day. The primary end point was the progression-free survival (PFS) rate at 16 weeks. Secondary end points included objective response rate, clinical benefit rate, 2-year overall survival rate, safety, and changes in levels of bone resorption/formation biomarkers.Results: Seventy-three patients were enrolled and treated. Median time from diagnosis of metastatic disease to initiation of bosutinib treatment was 24.5 months. For the intent-to-treat population, the PFS rate at 16 weeks was 39.6%. Unexpectedly, all responding patients (n = 4) were hormone receptor positive. The clinical benefit rate was 27.4%. The 2-year overall survival rate was 26.4%. The main toxic effects were diarrhea (66%), nausea (55%), and vomiting (47%). Grade 3-4 laboratory aminotransferase elevations occurred in 14 (19%) patients. Myelosuppression was minimal. No consistent changes in the levels of bone resorption/formation biomarkers were seen.Conclusions: Bosutinib showed promising efficacy in prolonging time to progression in chemotherapy-pretreated patients with locally advanced or metastatic breast cancer. Bosutinib was generally well tolerated, with a safety profile different from that of the Src/Abl tyrosine kinase inhibitor dasatinib in a similar patient population.