Department of Medical Oncology, San Raffaele Scientific Institute, Milano, Italy.
Department of Oncology, Azienda Sanitaria Universitaria Integrata, Udine, Italy.
JAMA Oncol. 2018 Mar 1;4(3):302-308. doi: 10.1001/jamaoncol.2017.4612.
Studies of neoadjuvant chemotherapy regimens using anthracyclines followed by taxanes have reported a doubling of pathological complete remission (pCR) rates compared with anthracycline-based regimens alone. A reverse sequence did not reduce activity. Nab-paclitaxel is an albumin-bound nanoparticle of paclitaxel that allows for safe infusion without premedication, and its use led to a significantly higher rate of pCR in the GeparSepto trial.
To determine whether nab-paclitaxel improves the outcomes of early and locally advanced human epidermal growth factor receptor 2 (ERBB2/HER2)-negative breast cancer compared with paclitaxel when delivered in a neoadjuvant setting.
DESIGN, SETTING, AND PARTICIPANTS: In this multicenter, open-label study, in collaboration with Grupo Español de Investigación en Cáncer de Mama (GEICAM) and Breast Cancer Research Center-Western Australia (BCRC-WA), patients with newly diagnosed and centrally confirmed ERBB2/HER2-negative breast cancer were recruited. Participants were randomly allocated to paclitaxel, 90 mg/m2 (349 patients), or nab-paclitaxel, 125 mg/m2 (346 patients). The 2 drugs were given on weeks 1, 2, and 3 followed by 1 week of rest for 4 cycles before 4 cycles of an anthracycline regimen per investigator choice.
The primary end point was the rate of pCR, defined as absence of invasive cells in the breast and axillary nodes (ie, ypT0/is ypN0) at the time of surgery. A secondary end point was to assess tolerability and safety of the 2 regimens.
From May 2013 to March 2015, 814 patients were registered to the study; 695 patients met central confirmation eligibility and were randomly allocated to receive either paclitaxel (349), or nab-paclitaxel (346) (median age, 50 years; range, 25-79 years). The intention-to-treat analysis of the primary end point pCR revealed that the improved pCR rate after nab-paclitaxel (22.5%) was not statistically significant compared with paclitaxel (18.6%; odds ratio [OR], 0.77; 95% CI, 0.52-1.13; P = .19). Overall, 38 of 335 patients (11.3%) 11.3% of patients had at least 1 serious adverse event in the paclitaxel arm and 54 of 337 patient (16.0%) in the nab-paclitaxel arm. Peripheral neuropathy of grade 3 or higher occurred in 6 of 335 patients (1.8%) and in 15 of 337 (4.5%), respectively.
The improved rate of pCR after nab-paclitaxel was not statistically significant. The multivariate analysis revealed that tumor subtype (triple-negative vs luminal B-like) was the most significant factor (OR, 4.85; 95% CI, 3.28-7.18) influencing treatment outcome.
clinicaltrials.gov Identifier: NCT01822314.
重要性： 采用蒽环类药物联合紫杉烷类药物的新辅助化疗方案与仅采用蒽环类药物的方案相比，病理完全缓解（pCR）率提高了一倍。相反的顺序并没有降低活性。白蛋白结合型紫杉醇（nab-紫杉醇）是一种紫杉醇的纳米颗粒，可在无需预处理的情况下安全输注，其在 GeparSepto 试验中的使用显著提高了 pCR 率。
目的： 确定在新辅助环境中使用 nab-紫杉醇与紫杉醇相比，是否能提高人表皮生长因子受体 2（ERBB2/HER2）阴性早期和局部晚期乳腺癌的治疗效果。
设计、地点和参与者： 在这项与西班牙乳腺癌研究组（GEICAM）和西澳乳腺癌研究中心（BCRC-WA）合作进行的多中心、开放标签研究中，招募了新诊断且经中心确认的 ERBB2/HER2 阴性乳腺癌患者。参与者被随机分配接受紫杉醇，90mg/m2（349 例）或 nab-紫杉醇，125mg/m2（346 例）。这两种药物在第 1、2 和 3 周给药，每 3 周休息 1 周，共 4 个周期，然后根据研究者的选择进行 4 个周期的蒽环类药物方案。
主要终点和措施： 主要终点是 pCR 率，定义为手术时乳房和腋窝淋巴结中无浸润细胞（即 ypT0/is ypN0）。次要终点是评估两种方案的耐受性和安全性。
结果： 2013 年 5 月至 2015 年 3 月，共有 814 名患者登记参加了该研究；695 名患者符合中心确认的入选标准，并随机分配接受紫杉醇（349 例）或 nab-紫杉醇（346 例）治疗（中位年龄 50 岁，范围 25-79 岁）。对主要终点 pCR 的意向治疗分析显示，nab-紫杉醇（22.5%）改善的 pCR 率与紫杉醇（18.6%）相比没有统计学意义（比值比 [OR]，0.77；95%置信区间 [CI]，0.52-1.13；P=0.19）。总体而言，紫杉醇组有 38 例（11.3%）患者至少有 1 例严重不良事件，nab-紫杉醇组有 54 例（16.0%）患者至少有 1 例严重不良事件。紫杉醇组有 6 例（1.8%）和 nab-紫杉醇组有 15 例（4.5%）患者发生 3 级或以上周围神经病变。
结论和相关性： nab-紫杉醇改善 pCR 率无统计学意义。多变量分析显示，肿瘤亚型（三阴性与 luminal B 样）是影响治疗效果的最显著因素（OR，4.85；95%CI，3.28-7.18）。
试验注册： clinicaltrials.gov 标识符：NCT01822314。
