Medical Oncology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Medical Oncology Department, Institut de Cancérologie de l'Ouest, Saint-Herblain, France.
Ann Oncol. 2018 May 1;29(5):1195-1202. doi: 10.1093/annonc/mdy063.
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 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.
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%).
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.
卡培他滨是一种已被批准的标准疗法，适用于蒽环类和紫杉烷类预处理后的局部晚期或转移性乳腺癌（BC）。在这种情况下，长春氟宁在 II 期研究中显示出单药活性，并且与卡培他滨联合使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。
局部复发性/转移性 BC 患者既往接受过蒽环类和紫杉烷类治疗或耐药，随机分配至长春氟宁（280mg/m2，第 1 天）加口服卡培他滨[825mg/m2，每日 2 次（b.i.d.），第 1-14 天]，每 3 周（q3w）或单药口服卡培他滨（1250mg/m2，b.i.d.，第 1-14 天）q3w。主要终点是无进展生存期（PFS），由独立审查委员会评估。该研究有 90%的效能检测 PFS 提高 30%。
总体而言，770 名患者被随机分配。与卡培他滨单药治疗相比，VC 治疗的 PFS 显著延长[风险比，0.84，95%置信区间（CI），0.71-0.99；对数秩 P=0.043；中位 PFS 分别为 5.6 个月和 4.3 个月]。与卡培他滨单药治疗相比，VC 组和卡培他滨单药组的中位总生存期分别为 13.9 个月和 11.7 个月[风险比，0.98；95%CI，0.83-1.15；对数秩 P=0.77]。两组间生活质量无差异。联合治疗组最常见的不良事件（NCI CTCAE 版本 3.0）为血液学和胃肠道不良事件。VC 组中性粒细胞减少症 4 级更为常见（12%比卡培他滨单药组 1%）；发热性中性粒细胞减少症分别为 2%和 0.5%。VC 组手足综合征发生率较低（3 级：卡培他滨单药组 19%，VC 组 4%）。周围神经病变在两组中均不常见（3 级：卡培他滨单药组 0.3%，VC 组 1%）。
与卡培他滨单药治疗相比，长春氟宁联合卡培他滨在蒽环类和紫杉烷类预处理后的局部复发性/转移性 BC 患者中，PFS 略有改善，安全性可接受。
临床试验.gov：NCT01095003。
