2016年，英国《柳叶刀》肿瘤学分册发表的德国乳腺癌协作组（GBG）第69号研究（GeparSepto）短期结果表明，每周白蛋白紫杉醇（白蛋白结合型纳米微粒紫杉醇）与每周溶剂型紫杉醇相比，可以显著提高早期乳腺癌患者术前表柔比星＋环磷酰胺新辅助治疗的病理完全缓解率（38%比29%，P=0.00065）。
2019年5月13日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表GBG、柏林赫利俄斯医院、奥芬巴赫萨那医院、海德堡大学国家肿瘤疾病中心、卡塞尔圣伊丽莎白医院、莱比锡妇女医院、柏林大学医学院、基尔大学医院、哈姆圣芭芭拉医院、埃森米特医院、科隆霍伟德医院、埃尔兰根大学医院、比勒费尔德肿瘤医院、慕尼黑红十字会医院、威滕马里安医院、柏林大学妇女医院、科隆大学医院、罗斯托克大学妇女医院、乌尔姆大学医院的GBG-69研究（GeparSepto）长期结局报告，比较了白蛋白紫杉醇与溶剂型紫杉醇术前新辅助治疗早期乳腺癌患者的生存。
GeparSepto: Nanoparticle-based Paclitaxel vs Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Early Breast Cancer (NCT01583426)
该德国多中心随机对照III期研究于2012年7月30日～2013年12月23日从德国69个研究中心入组组织学证实原发性乳腺癌患者，按1∶1的比例随机分配接受12次每周白蛋白紫杉醇150mg/m²（2013年3月28日研究方案被修订后改为125mg/m²）或每周溶剂型紫杉醇80mg/m²，同时给予4次每3周表柔比星90mg/m²＋环磷酰胺600mg/m²。对于HER2阳性乳腺癌患者，同时给予曲妥珠单抗（首次8mg/kg，随后每3周6mg/kg）＋帕妥珠单抗（首次840mg，随后每3周420mg）双抗体治疗持续1年。
结果，开始治疗患者共计1206例，其中白蛋白紫杉醇组606例、溶剂型紫杉醇组600例。中位随访49.6个月（范围0.5～64.0个月）后，发生无浸润病变生存事件243例（溶剂型紫杉醇组143例，白蛋白紫杉醇组100例）。
4年时，白蛋白紫杉醇组与溶剂型紫杉醇组的患者相比：
无浸润病变生存率显著较高（84.0%比76.3%，风险比：0.66，95%置信区间：0.51～0.86，P=0.002）
总生存率无统计学显著差异（89.7%比87.2%，风险比：0.82，95%置信区间：0.59～1.16，P=0.260）
治疗相关外周感觉神经病变的长期随访结果表明，白蛋白紫杉醇125mg/m²与白蛋白紫杉醇150mg/m²相比，外周感觉神经病变由2～4级缓解为1级的中位时间显著较短（6.4比12.7周，P=0.014）。
因此，该研究结果表明，白蛋白紫杉醇与溶剂型紫杉醇相比，早期乳腺癌患者的病理完全缓解率、无浸润病变生存率显著提高，总生存率相似。白蛋白紫杉醇125mg/m²与白蛋白紫杉醇150mg/m²相比，外周感觉神经病变改善较快。
J Clin Oncol. 2019 May 13. [Epub ahead of print]
NAB-Paclitaxel Improves Disease-Free Survival in Early Breast Cancer: GBG 69-GeparSepto.
Michael Untch, Christian Jackisch, Andreas Schneeweiss, Sabine Schmatloch, Bahriye Aktas, Carsten Denkert, Christian Schem, Hermann Wiebringhaus, Sherko Kümmel, Mathias Warm, Peter A. Fasching, Marianne Just, Claus Hanusch, John Hackmann, Jens-Uwe Blohmer, Kerstin Rhiem, Wolfgang D. Schmitt, Jenny Furlanetto, Bernd Gerber, Jens Huober, Valentina Nekljudova, Gunter von Minckwitz, Sibylle Loibl.
Helios Klinikum Berlin-Buch, Berlin, Germany; Sana Klinikum, Offenbach, Germany; Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany; St Elisabeth Krankenhaus Kassel, Kassel, Germany; Klinik und Poliklinik für Frauenheilkunde Leipzig, Leipzig, Germany; Charité-Universitatsmedizin Berlin, Berlin, Germany; Universitatsklinikum Kiel, Kiel, Germany; St Barbara-Klinik Hamm-Heessen, Hamm, Germany; Interdisziplinares Brustzentrum an den Kliniken Essen-Mitte, Essen, Germany; Brustzentrum im Krankenhaus Koln-Holweide, Cologne, Germany; Universitatsklinikum Erlangen, Erlangen, Germany; Onkologische Schwerpunktpraxis Bielefeld, Bielefeld, Germany; Klinikum zum Roten Kreuz, Munich, Germany; Marien Hospital Witten, Witten, Germany; Klinik für Gynakologie am Campus Charité Mitte, Berlin, Germany; Uniklinik Koln, Cologne, Germany; German Breast Group, Neu-Isenburg, Germany; Universitats-Frauenklinik, Rostock, Germany; Universitatsklinikum Ulm, Ulm, Germany.
PURPOSE: 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.
METHODS: Patients with histologically confirmed primary BC were randomly assigned in a 1:1 ratio to 12 times weekly NAB-paclitaxel 150 mg/m² (after study amendment, 125 mg/m²) or weekly sb-paclitaxel 80 mg/m² followed in both arms by four times epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² 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.
RESULTS: 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% v 76.3%; hazard ratio, 0.66; 95% CI, 0.51 to 0.86; P = .002), whereas overall survival did not significantly differ between the two treatment arms (89.7% v 87.2%, respectively; hazard ratio, 0.82; 95% CI, 0.59 to 1.16; P = .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/m² compared with NAB-paclitaxel 150 mg/m².
CONCLUSION: 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/m² compared with NAB-paclitaxel 150 mg/m².
DOI: 10.1200/JCO.18.01842
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