2016年，英國《柳葉刀》腫瘤學(xué)分冊發(fā)表的德國乳腺癌協(xié)作組（GBG）第69號研究（GeparSepto）短期結(jié)果表明，每周白蛋白紫杉醇（白蛋白結(jié)合型納米微粒紫杉醇）與每周溶劑型紫杉醇相比，可以顯著提高早期乳腺癌患者術(shù)前表柔比星＋環(huán)磷酰胺新輔助治療的病理完全緩解率（38%比29%，P=0.00065）。
2019年5月13日，美國臨床腫瘤學(xué)會《臨床腫瘤學(xué)雜志》在線發(fā)表GBG、柏林赫利俄斯醫(yī)院、奧芬巴赫薩那醫(yī)院、海德堡大學(xué)國家腫瘤疾病中心、卡塞爾圣伊麗莎白醫(yī)院、萊比錫婦女醫(yī)院、柏林大學(xué)醫(yī)學(xué)院、基爾大學(xué)醫(yī)院、哈姆圣芭芭拉醫(yī)院、埃森米特醫(yī)院、科隆霍偉德醫(yī)院、埃爾蘭根大學(xué)醫(yī)院、比勒費(fèi)爾德腫瘤醫(yī)院、慕尼黑紅十字會醫(yī)院、威滕馬里安醫(yī)院、柏林大學(xué)婦女醫(yī)院、科隆大學(xué)醫(yī)院、羅斯托克大學(xué)婦女醫(yī)院、烏爾姆大學(xué)醫(yī)院的GBG-69研究（GeparSepto）長期結(jié)局報告，比較了白蛋白紫杉醇與溶劑型紫杉醇術(shù)前新輔助治療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)
該德國多中心隨機(jī)對照III期研究于2012年7月30日～2013年12月23日從德國69個研究中心入組組織學(xué)證實(shí)原發(fā)性乳腺癌患者，按1∶1的比例隨機(jī)分配接受12次每周白蛋白紫杉醇150mg/m2（2013年3月28日研究方案被修訂后改為125mg/m2）或每周溶劑型紫杉醇80mg/m2，同時給予4次每3周表柔比星90mg/m2＋環(huán)磷酰胺600mg/m2。對于HER2陽性乳腺癌患者，同時給予曲妥珠單抗（首次8mg/kg，隨后每3周6mg/kg）＋帕妥珠單抗（首次840mg，隨后每3周420mg）雙抗體治療持續(xù)1年。
結(jié)果，開始治療患者共計(jì)1206例，其中白蛋白紫杉醇組606例、溶劑型紫杉醇組600例。中位隨訪49.6個月（范圍0.5～64.0個月）后，發(fā)生無浸潤病變生存事件243例（溶劑型紫杉醇組143例，白蛋白紫杉醇組100例）。
4年時，白蛋白紫杉醇組與溶劑型紫杉醇組的患者相比：
無浸潤病變生存率顯著較高（84.0%比76.3%，風(fēng)險比：0.66，95%置信區(qū)間：0.51～0.86，P=0.002）
總生存率無統(tǒng)計(jì)學(xué)顯著差異（89.7%比87.2%，風(fēng)險比：0.82，95%置信區(qū)間：0.59～1.16，P=0.260）
治療相關(guān)外周感覺神經(jīng)病變的長期隨訪結(jié)果表明，白蛋白紫杉醇125mg/m2與白蛋白紫杉醇150mg/m2相比，外周感覺神經(jīng)病變由2～4級緩解為1級的中位時間顯著較短（6.4比12.7周，P=0.014）。
因此，該研究結(jié)果表明，白蛋白紫杉醇與溶劑型紫杉醇相比，早期乳腺癌患者的病理完全緩解率、無浸潤病變生存率顯著提高，總生存率相似。白蛋白紫杉醇125mg/m2與白蛋白紫杉醇150mg/m2相比，外周感覺神經(jīng)病變改善較快。
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
