Helios Klinikum Berlin-Buch, Berlin, Germany.
Sana Klinikum, Offenbach, Germany.
J Clin Oncol. 2019 Sep 1;37(25):2226-2234. doi: 10.1200/JCO.18.01842. Epub 2019 May 13.
The GeparSepto trial demonstrated that weekly nanoparticle albumin-bound (NAB)-paclitaxel significantly improves the pathologic complete remission rate compared with weekly solvent-based (sb) paclitaxel followed by epirubicin plus cyclophosphamide as neoadjuvant treatment in patients with primary breast cancer (BC). Here, we report data on long-term outcomes.
Patients with histologically confirmed primary BC were randomly assigned in a 1:1 ratio to 12 times weekly NAB-paclitaxel 150 mg/m (after study amendment, 125 mg/m) or weekly sb-paclitaxel 80 mg/m followed in both arms by four times epirubicin 90 mg/m plus cyclophosphamide 600 mg/m every 3 weeks. Patients with human epidermal growth factor receptor 2 (HER2)-positive BC received dual antibody treatment with trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks) and pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks) concurrently to chemotherapy and continued for 1 year.
A total of 1,206 patients started treatment, 606 with NAB-paclitaxel and 600 with sb-paclitaxel. After a median follow-up of 49.6 months (range, 0.5 to 64.0 months), 243 invasive disease-free survival (iDFS) events were reported (143 in the sb-paclitaxel and 100 in the NAB-paclitaxel arm). At 4 years, overall patients treated with NAB-paclitaxel had a significantly better iDFS compared with sb-paclitaxel (84.0% 76.3%; hazard ratio, 0.66; 95% CI, 0.51 to 0.86; = .002), whereas overall survival did not significantly differ between the two treatment arms (89.7% 87.2%, respectively; hazard ratio, 0.82; 95% CI, 0.59 to 1.16; = .260). Long-term follow-up of the treatment-related peripheral sensory neuropathy (PSN) showed a significant decrease of the median time to resolve PSN after NAB-paclitaxel 125 mg/m compared with NAB-paclitaxel 150 mg/m.
The significantly higher pathologic complete response rate with NAB-paclitaxel translated into a significantly improved iDFS in patients with early BC as compared with sb-paclitaxel. PSN improved much faster under NAB-paclitaxel 125 mg/m compared with NAB-paclitaxel 150 mg/m.
GeparSepto 试验表明，与每周溶剂型（sb）紫杉醇联合表柔比星和环磷酰胺新辅助治疗相比，每周纳米白蛋白结合紫杉醇（NAB-紫杉醇）可显著提高原发性乳腺癌（BC）患者的病理完全缓解率。在此，我们报告了长期结果的数据。
经组织学证实的原发性 BC 患者以 1:1 的比例随机分配，接受 12 次每周 NAB-紫杉醇 150mg/m（研究修订后为 125mg/m）或每周 sb-紫杉醇 80mg/m，之后两组均接受 4 次表柔比星 90mg/m 和环磷酰胺 600mg/m，每 3 周一次。HER2 阳性 BC 患者接受曲妥珠单抗（8mg/kg 负荷剂量，随后每 3 周 6mg/kg）和帕妥珠单抗（840mg 负荷剂量，随后每 3 周 420mg）双重抗体治疗与化疗同时进行，并持续 1 年。
共有 1206 例患者开始治疗，606 例接受 NAB-紫杉醇治疗，600 例接受 sb-紫杉醇治疗。中位随访 49.6 个月（范围 0.5 至 64.0 个月）后，报告了 243 例浸润性无病生存（iDFS）事件（sb-紫杉醇组 143 例，NAB-紫杉醇组 100 例）。4 年时，接受 NAB-紫杉醇治疗的患者总体 iDFS 明显优于 sb-紫杉醇（84.0% vs 76.3%；风险比，0.66；95%CI，0.51 至 0.86；=0.002），而两组的总生存无显著差异（89.7% vs 87.2%；风险比，0.82；95%CI，0.59 至 1.16；=0.260）。长期随访的治疗相关周围感觉神经病变（PSN）显示，与 NAB-紫杉醇 150mg/m 相比，NAB-紫杉醇 125mg/m 后 PSN 缓解的中位时间明显缩短。
与 sb-紫杉醇相比，NAB-紫杉醇更高的病理完全缓解率转化为早期 BC 患者显著提高的 iDFS。与 NAB-紫杉醇 150mg/m 相比，NAB-紫杉醇 125mg/m 下 PSN 改善速度更快。
