Oncology Department, Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain
Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, Spain, on behalf of GEICAM (Spanish Breast Cancer Group), Spain.
Oncologist. 2017 Nov;22(11):1301-1308. doi: 10.1634/theoncologist.2017-0052. Epub 2017 Jul 12.
Nanoparticle albumin-bound paclitaxel (nab-Paclitaxel) is an alternative to standard taxanes for breast cancer (BC) treatment. We evaluated nab-Paclitaxel efficacy as neoadjuvant treatment for early estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) disease.
Women with ER+, HER2-, stage II-III BC were treated preoperatively with four cycles of weekly nab-Paclitaxel (150 mg/m), 3 weeks on and 1 week off. We hypothesized that poor pathological response rate (residual cancer burden [RCB] III; Symmans criteria) would be ≤16%.
Eighty-one patients with a median age of 47 years were treated; 64.2% were premenopausal, and 69% of tumors were stage II. Residual cancer burden III rate was 28.4% (95% confidence interval [CI]: 18.6%-38.2%), RCB 0+I (good response) rate was 24.7% (95% CI: 15.3%-34.1%) and RCB 0 (complete response) rate was 7.4% (95% CI: 1.7%-13.1%). Objective response rate by magnetic resonance imaging was 76.5% and rate of conversion to breast conserving surgery was 40.0%. The most frequent grade 3 and 4 toxicity was neutropenia (12.3% and 3.7% of patients, respectively), without any febrile neutropenia. Sensory neuropathy grade 2 and 3 were seen in 25.9% and 2.5% of patients, respectively. Tumor secreted protein, acidic, cysteine-rich (SPARC) overexpression was significantly associated with RCB 0 (odds ratio: 0.079; 95% CI: 0.009-0.689; = .0216).
Despite failing to confirm an RCB III rate ≤16% in nab-Paclitaxel-treated patients, the RCB 0+I rate indicates a significant drug antitumor activity with low rates of grade 3-4 toxicity. Our exploratory biomarker analysis suggests a potential predictive role of complete response for SPARC. Confirmatory analyses are warranted, adapting dose and schedule to decrease peripheral neurotoxicity. (Trial registration: European Clinical Trials Database study number: 2011-004476-10; ClinicalTrials.gov: NCT01565499).
The pathological response rate (residual cancer burden [RCB]; Symmans criteria) of nanoparticle albumin-bound paclitaxel administered as neoadjuvant treatment for early estrogen receptor-positive, human epidermal growth factor receptor 2-negative disease was evaluated. Whereas poor response (RCB III) was 24.7%, similar to that for docetaxel, good response (RCB 0+I) reached 23.0%, far superior to the 13% for docetaxel, while keeping toxicity low. Exploratory biomarker analysis suggests secreted protein, acidic, cysteine-rich overexpression in tumor cells as a potential predictor of complete response (RCB 0). Findings point to an encouraging single-agent neoadjuvant treatment with low toxicity, which warrants future research and development.
纳米白蛋白结合紫杉醇（nab-紫杉醇）是治疗乳腺癌（BC）的标准紫杉醇类药物的替代药物。我们评估了 nab-紫杉醇作为早期雌激素受体阳性（ER+）、人表皮生长因子受体 2 阴性（HER2-）疾病新辅助治疗的疗效。
患有 II-III 期 ER+、HER2- BC 的女性接受了四个周期的每周 nab-紫杉醇（150mg/m）治疗，每 3 周一次，1 周休息。我们假设病理反应率差（残留癌负担[RCB]III；Symmans 标准）≤16%。
共 81 例中位年龄为 47 岁的患者接受了治疗；64.2%为绝经前，69%的肿瘤为 II 期。RCB III 率为 28.4%（95%置信区间[CI]：18.6%-38.2%），RCB 0+I（良好反应）率为 24.7%（95%CI：15.3%-34.1%），RCB 0（完全缓解）率为 7.4%（95%CI：1.7%-13.1%）。磁共振成像的客观反应率为 76.5%，保乳手术转化率为 40.0%。最常见的 3 级和 4 级毒性为中性粒细胞减少症（分别为 12.3%和 3.7%的患者），无发热性中性粒细胞减少症。感觉神经病变 2 级和 3 级分别见于 25.9%和 2.5%的患者。肿瘤分泌蛋白、酸性、富含半胱氨酸（SPARC）过表达与 RCB 0 显著相关（优势比：0.079；95%CI：0.009-0.689；=0.0216）。
尽管未能证实 nab-紫杉醇治疗患者的 RCB III 率≤16%，但 RCB 0+I 率表明药物具有显著的抗肿瘤活性，且 3-4 级毒性发生率较低。我们的探索性生物标志物分析表明，SPARC 完全缓解可能具有潜在的预测作用。需要进行确证性分析，以适应剂量和方案，降低周围神经毒性。（试验注册：欧洲临床试验数据库研究编号：2011-004476-10；ClinicalTrials.gov：NCT01565499）。
评估了纳米白蛋白结合紫杉醇作为早期雌激素受体阳性、人表皮生长因子受体 2 阴性疾病新辅助治疗的病理反应率（残留癌负担[RCB]；Symmans 标准）。尽管不良反应（RCB III）为 24.7%，与多西紫杉醇相似，但良好反应（RCB 0+I）达到 23.0%，远高于多西紫杉醇的 13%，同时保持低毒性。探索性生物标志物分析表明，肿瘤细胞中富含酸性、半胱氨酸的分泌蛋白过表达可能是完全缓解（RCB 0）的潜在预测因子。研究结果表明，nab-紫杉醇具有令人鼓舞的单一药物新辅助治疗作用，毒性低，值得进一步研究和开发。
