Background: 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.
Materials and methods: Women with ER+, HER2-, stage II-III BC were treated preoperatively with four cycles of weekly nab-Paclitaxel (150 mg/m2), 3 weeks on and 1 week off. We hypothesized that poor pathological response rate (residual cancer burden [RCB] III; Symmans criteria) would be ≤16%.
Results: 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; p = .0216).
Conclusion: 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).
Implications for practice: 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.
摘要
背景.纳米微粒白蛋白结合型紫杉醇（nab‐紫杉醇）是乳腺癌（BC）标准紫杉烷类药物治疗的替代疗法。研究评价了nab‐紫杉醇作为新辅助疗法治疗早期雌激素受体‐阳性（ER+）、人表皮生长因子受体2‐阴性（HER2‐）的疗效。
材料与方法.罹患ER+、HER2‐、II–III期BC的女性在术前接受4个周期的nab‐紫杉醇（150 mg/m2, 每周一次）治疗, 每个周期用药3周, 停药1周。假设缓解率≤16%为病理学缓解不佳 [残癌负荷（RCB）III级, Symmans标准]。
结果：81名患者（中位年龄为47岁）接受治疗；64.2%的患者为绝经前女性, 69%为II期乳腺癌患者。RCB III级的比率为28.4%[95%置信区间（CI）：18.6%–38.2%], RCB 0+I级（明显缓解）的比率为24.7%（95% CI：15.3%–34.1%）, RCB 0级（完全缓解）的比率为7.4%（95% CI：1.7%–13.1%）。经磁共振成像确定的客观缓解率为76.5%, 转为接受乳腺癌保乳手术的比率为40.0%。最常见的3‐4级毒性反应为中性粒细胞减少症（分别为12.3%及3.7%）, 未发生中性粒细胞减少性发热。2‐3级感觉神经病变分别见于25.9%及2.5%的患者。肿瘤富含半胱氨酸酸性分泌蛋白（SPARC）过表达与RCB 0级显著相关（比值比：0.079, 95% CI：0.009–0.689; p = 0.0216）。
结论.虽然未能证实nab‐紫杉醇治疗的患者的RCB III级比率≤16%, 但RCB 0+I级比率表明该药物明显具有抗肿瘤活性, 且3‐4级毒性的发生率较低。探索性生物标志物分析表明, SPARC对完全缓解具有潜在预测作用。需要进行验证性分析, 通过调整给药剂量和时间来减轻周围神经毒性。（试验注册：欧洲临床试验数据库研究编号：2011‐004476‐10;
Keywords: Estrogen receptor‐positive breast cancer; Luminal breast cancer; Nanoparticle albumin‐bound Paclitaxel; Neoadjuvant treatment; Residual cancer burden.
© AlphaMed Press 2017.