Background There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC. Patients and methods In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m2 intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS). Results A total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P = 0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P = 0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P = 0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%). Conclusions Vinflunine 280 mg/m2 q3w did not improve OS compared with the physician's choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m2 merits evaluation. ClinicalTrials.gov NCT01091168.

中文翻译：

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在长期大量治疗的转移性乳腺癌患者中，长春氟宁与烷化剂的开放标签随机III期试验。

背景技术对于转移性乳腺癌（MBC），二线化疗进展后尚无标准治疗方法。我们将长效MBC患者中的长春氟宁与医师选择的烷化剂（AA）进行了比较。患者和方法在这项开放标签的III期试验中，MBC患者如果已接受至少两种先前的MBC化疗方案并接受了蒽环类，紫杉烷，抗代谢药物和长春花生物碱治疗，则将其包括在内。由于耐药性和/或不耐受性，患者不再是这些化学疗法的候选人。患者每3周随机（q3w）静脉注射长春氟宁280 mg / m2或q3w AA单药治疗。分层因素为生产状况，MBC先前的化学疗法行数，疾病可测量性和研究地点。主要终点是总体生存期（OS）。结果共有594例患者被随机分组​​（298例为长春氟宁，296例为AA）。OS的各治疗组之间无差异（危险比1.04，P = 0.67；长春氟宁中位数为9.1个月，AA为9.3个月），无进展生存期（危险比0.94，P = 0.49；中位数为2.5个月与1.9个月）或总体响应率（分别为6％和4％）。但是，长春氟宁的疾病控制率显着高于AA（分别为44％和35％； P = 0.04）。最常见的不良事件（任何级别）是血液和胃肠道疾病以及两臂乏力。最常见的3/4级不良事件是中性粒细胞减少（分别为19％和11％，长春氟宁和AA）和乏力（10％对4％）。结论与医生选择AA作为MBC的三线或后继疗法相比，Vinflunine 280 mg / m2 q3w不能改善OS。长春氟宁显示出可接受的安全性，表明长春氟宁320 mg / m2值得评估。ClinicalTrials.gov NCT01091168。