Background Capecitabine is an approved standard therapy for anthracycline- and taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine has demonstrated single-agent activity in phase II studies in this setting and activity and tolerability when combined with capecitabine. We compared the combination of vinflunine plus capecitabine (VC) with single-agent capecitabine. Patients and methods Patients with locally recurrent/metastatic BC previously treated or resistant to an anthracycline and resistant to taxane therapy were randomly assigned to either vinflunine (280 mg/m2, day 1) plus oral capecitabine [825 mg/m2 twice daily (b.i.d.), days 1-14] every 3 weeks (q3w) or single-agent oral capecitabine (1250 mg/m2 b.i.d., days 1-14) q3w. The primary end point was progression-free survival (PFS) assessed by an independent review committee. The study had 90% power to detect a 30% improvement in PFS. Results Overall, 770 patients were randomised. PFS was significantly longer with VC than with capecitabine alone [hazard ratio, 0.84, 95% confidence interval (CI), 0.71-0.99; log-rank P = 0.043; median 5.6 versus 4.3 months, respectively]. Median overall survival was 13.9 versus 11.7 months with VC versus capecitabine alone, respectively (hazard ratio, 0.98; 95% CI, 0.83-1.15; log-rank P = 0.77). No difference in quality of life was observed between the two treatment arms. The most common adverse events (NCI CTCAE version 3.0) in the combination arm were haematological and gastrointestinal. Grade 4 neutropenia was more frequent with VC (12% versus 1% with capecitabine alone); febrile neutropenia occurred in 2% versus 0.5%, respectively. Hand-foot syndrome was less frequent with VC (grade 3: 4% versus 19% for capecitabine alone). Peripheral neuropathy was uncommon in both arms (grade 3: 1% versus 0.3%). Conclusions Vinflunine combined with capecitabine demonstrated a modest improvement in PFS and an acceptable safety profile compared with capecitabine alone in patients with anthracycline- and taxane-pretreated locally recurrent/metastatic BC. ClinicalTrials.gov NCT01095003.

中文翻译：

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长春氟宁加卡培他滨与单用卡培他滨对先前用蒽环类药物治疗并对紫杉烷有抗药性的晚期乳腺癌患者的随机III期试验。

背景卡培他滨是蒽环类和紫杉烷类预处理的局部晚期或转移性乳腺癌（BC）的公认标准治疗方法。长春氟宁已在这种环境下的II期研究中证明了单药活性，与卡培他滨合用时具有活性和耐受性。我们比较了长春氟宁加卡培他滨（VC）与单药卡培他滨的组合。患者和方法将先前接受过蒽环类药物治疗或耐药，对紫杉类药物耐药的局部复发/转移性BC患者随机分为长春氟宁（280 mg / m2，第1天）加口服卡培他滨[825 mg / m2，每天两次（出价） ，第1-14天]每3周一次（q3w）或单剂口服卡培他滨（1250 mg / m2投标，第1-14天）q3w。主要终点是由独立评审委员会评估的无进展生存期（PFS）。该研究具有90％的功效可检测出PFS改善30％。结果共有770例患者被随机分组​​。VC组的PFS明显比单独使用卡培他滨的组长[危险比，0.84，95％置信区间（CI），0.71-0.99；对数秩P = 0.043; 中位数分别为5.6个月和4.3个月]。中位总生存期分别为13.9个月和11.7个月（分别为VC和卡培他滨）（危险比，0.98； 95％CI，0.83-1.15；对数秩P = 0.77）。在两个治疗组之间没有观察到生活质量的差异。联合用药中最常见的不良事件（NCI CTCAE 3.0版）是血液学和胃肠道疾病。VC发生4级中性粒细胞减少症的频率更高（分别为12％和1％卡培他滨）。发热性中性粒细胞减少症的发生率分别为2％和0.5％。VC患手足综合征的频率较低（3级：4％，而卡培他滨仅19％）。两组的周围神经病变都不常见（3级：1％对0.3％）。结论与单独使用卡培他滨的患者相比，在蒽环类和紫杉烷预处理的局部复发/转移性BC患者中，长春氟宁联合卡培他滨显示出PFS的适度改善和可接受的安全性。ClinicalTrials.gov NCT01095003。结论与单独使用卡培他滨的患者相比，在蒽环类和紫杉烷预处理的局部复发/转移性BC患者中，长春氟宁联合卡培他滨显示出PFS的适度改善和可接受的安全性。ClinicalTrials.gov NCT01095003。结论与单独使用卡培他滨的患者相比，在蒽环类和紫杉烷预处理的局部复发/转移性BC患者中，长春氟宁联合卡培他滨显示出PFS的适度改善和可接受的安全性。ClinicalTrials.gov NCT01095003。