First-line temozolomide combined with bevacizumab in metastatic melanoma: a multicentre phase II trial (SAKK 50/07)
First-line temozolomide combined with bevacizumab in metastatic melanoma: a multicentre phase II trial (SAKK 50/07)
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DOI：
10.1093/annonc/mdr126
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发表时间：
2012-02-01
影响因子：
50.5
通讯作者：
Dummer, R.
中科院分区：
文献类型：
--
作者：
von Moos, R.;Seifert, B.;Dummer, R.
背景：口服替莫唑胺在 III 期试验中显示出与达卡巴嗪相似的疗效，中位无进展生存期 (PFS) 为 2.1 个月。贝伐珠单抗对黑色素瘤和萌芽内皮细胞的增殖具有抑制作用。我们评估了在替莫唑胺中添加贝伐单抗以提高 IV 期黑色素瘤的疗效。 患者和方法：东部肿瘤合作组表现状态为 2 级或以上的既往未经治疗的转移性黑色素瘤患者接受替莫唑胺 150 mg/m 2 天第 1-7 次口服治疗和贝伐单抗 10 mg/kg 体重静脉注射治疗。每 2 周第 1 天，直至疾病进展或出现不可接受的毒性。主要终点是第 12 周时的疾病稳定率 [完全缓解 (CR)、部分缓解 (PR) 或疾病稳定 (SD)] (DSR12)；次要终点是最佳总体缓解、PFS、总体生存 (OS) 和不良事件。 结果：9 个瑞士中心招募了 62 名患者（中位年龄 59 岁）。 DSR12 为 52%（PR：10 名患者，SD：22 名患者）。确认的总体缓解率为 16.1%（CR：1 名患者，PR：9 名患者）。中位 PFS 和 OS 分别为 4.2 个月和 9.6 个月。 BRAF V600E 野生型患者的 OS（12.0 个月与 9.2 个月；P = 0.014）较高。结论：超过了主要终点，表明这种贝伐单抗/替莫唑胺组合具有良好的活性和良好的毒性特征。 BRAF 野生型患者的缓解率和 OS 显着更高。
Background: Oral temozolomide has shown similar efficacy to dacarbazine in phase III trials with median progression-free survival (PFS) of 2.1 months. Bevacizumab has an inhibitory effect on the proliferation of melanoma and sprouting endothelial cells. We evaluated the addition of bevacizumab to temozolomide to improve efficacy in stage IV melanoma.Patients and methods: Previously untreated metastatic melanoma patients with Eastern Cooperative Oncology Group performance status of two or more were treated with temozolomide 150 mg/m 2 days 1-7 orally and bevacizumab 10 mg/kg body weight i.v. day 1 every 2 weeks until disease progression or unacceptable toxicity. The primary end point was disease stabilisation rate [complete response (CR), partial response (PR) or stable disease (SD)] at week 12 (DSR12); secondary end points were best overall response, PFS, overall survival (OS) and adverse events.Results: Sixty-two patients (median age 59 years) enrolled at nine Swiss centres. DSR12 was 52% (PR: 10 patients and SD: 22 patients). Confirmed overall response rate was 16.1% (CR: 1 patient and PR: 9 patients). Median PFS and OS were 4.2 and 9.6 months. OS (12.0 versus 9.2 months; P = 0.014) was higher in BRAF V600E wild-type patients.Conclusions: The primary end point was surpassed showing promising activity of this bevacizumab/temozolomide combination with a favourable toxicity profile. Response and OS were significantly higher in BRAF wild-type patients.