Department of Medical Oncology, Division of Women's Cancers, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Breast Cancer Res Treat. 2013 Jun;139(2):403-10. doi: 10.1007/s10549-013-2551-9. Epub 2013 May 5.
We aimed to evaluate the efficacy and feasibility of combining trastuzumab/vinorelbine with bevacizumab in patients with first-or second-line HER2-positive, metastatic breast cancer (MBC). Eligible patients had HER2-positive measureable MBC, with no more than one prior line of chemotherapy, and were treated with trastuzumab (4 mg/kg × 2 mg/kg weekly thereafter), vinorelbine (25 mg/m(2) weekly), and bevacizumab (10 mg/kg every 2 weeks). Co-primary endpoints were (a) the proportion of patients alive and progression-free at 1 year and (b) safety profile/feasibility. Feasibility was defined as a rate of grade 3/4 non-hematologic toxicity attributable to protocol-based therapy <20 %. Twenty-nine patients were enrolled (n = 22 first-line, n = 7 second-line). Median age was 48 years (range 37-68). The median number of cycles received was 8 (1-23) and median duration on treatment was 7.4 months (range 1-22). The study was closed early due to higher-than-expected rates of grade 3/4 non-hematologic toxicities, with 50 events in 20 patients. A total of six patients (21 %) were taken off study for treatment-related toxicity. Most common treatment-related toxicities included fatigue (n = 7), febrile neutropenia (n = 4), and headache (n = 3). At 1 year, 8/22 first-line (36 %) and 2/7 second-line (29 %) patients were alive and progression-free. Median PFS was 9.9 months and 7.8 months in the first- and second-line cohorts, respectively. Objective responses were observed in 16/22 (73 %) and 5/7 (71 %) patients in the first- and second-line settings. Although the combination of vinorelbine, trastuzumab, and bevacizumab showed notable activity in HER2-positive MBC, the proportion of first-line patients alive and progression-free at 1 year was deemed unlikely to reach the pre-defined threshold for declaring success. Additionally, unacceptable toxicity was observed, at rates greater than previously reported with vinorelbine/trastuzumab or vinorelbine/bevacizumab doublet combinations.
我们旨在评估曲妥珠单抗/长春瑞滨联合贝伐珠单抗治疗一线或二线 HER2 阳性转移性乳腺癌（MBC）患者的疗效和可行性。符合条件的患者具有 HER2 阳性可测量 MBC，既往接受过不超过一线化疗，接受曲妥珠单抗（4 mg/kg×2 mg/kg 每周）、长春瑞滨（25 mg/m² 每周）和贝伐珠单抗（10 mg/kg 每 2 周）治疗。主要共同终点为（a）1 年时存活且无进展的患者比例和（b）安全性/可行性。可行性定义为归因于基于方案的治疗的 3/4 级非血液学毒性的发生率<20%。共入组 29 例患者（n=22 例一线治疗，n=7 例二线治疗）。中位年龄为 48 岁（范围 37-68）。中位接受的周期数为 8（1-23），中位治疗持续时间为 7.4 个月（范围 1-22）。由于 3/4 级非血液学毒性发生率高于预期，在 20 例患者中发生 50 例事件，研究提前结束。共有 6 例患者（21%）因治疗相关毒性而退出研究。最常见的治疗相关毒性包括疲劳（n=7）、发热性中性粒细胞减少症（n=4）和头痛（n=3）。1 年时，22 例一线治疗中有 8 例（36%）和 7 例二线治疗中有 2 例（29%）患者存活且无进展。一线和二线队列的中位 PFS 分别为 9.9 个月和 7.8 个月。在一线和二线治疗中，分别有 16/22（73%）和 5/7（71%）例患者观察到客观缓解。尽管长春瑞滨、曲妥珠单抗和贝伐珠单抗的联合治疗在 HER2 阳性 MBC 中显示出显著的活性，但 1 年时存活且无进展的一线患者比例被认为不太可能达到预先定义的成功标准。此外，观察到不可接受的毒性，其发生率高于先前报道的长春瑞滨/曲妥珠单抗或长春瑞滨/贝伐珠单抗双联治疗。
