NAB-Paclitaxel Improves Disease-Free Survival in Early Breast Cancer: GBG 69-GeparSepto

被引：111

作者：

Untch, Michael ^{[1
]}

Jackisch, Christian ^{[2
]}

Schneeweiss, Andreas ^{[3
]}

Schmatloch, Sabine ^{[4
]}

Aktas, Bahriye ^{[5
]}

Denkert, Carsten ^{[6
]}

Schem, Christian ^{[7
]}

Wiebringhaus, Hermann ^{[8
]}

Kuemmel, Sherko ^{[9
]}

Warm, Mathias ^{[10
]}

Fasching, Peter A. ^{[11
]}

Just, Marianne

Hanusch, Claus ^{[12
]}

Hackmann, John ^{[13
]}

Blohmer, Jens-Uwe ^{[14
]}

Rhiem, Kerstin ^{[15
]}

Schmitt, Wolfgang D. ^{[6
]}

Furlanetto, Jenny ^{[16
]}

Gerber, Bernd ^{[17
]}

Huober, Jens ^{[18
]}

Nekljudova, Valentina ^{[16
]}

von Minckwitz, Gunter ^{[16
]}

Loibl, Sibylle ^{[16
]}

机构：

[1] Helios Klinikum Berlin Buch, Berlin, Germany

[2] Sana Klinikum, Offenbach, Germany

[3] Natl Ctr Tumorerkrankungen, Heidelberg, Germany

[4] St Elisabeth Krankenhaus Kassel, Kassel, Germany

[5] Klin & Poliklin Frauenheilkunde Leipzig, Leipzig, Germany

[6] Charite Univ Med Berlin, Berlin, Germany

[7] Univ Klinikum Kiel, Kiel, Germany

[8] St Barbara Klin Hamm Heessen, Hamm, Germany

[9] Interdisziplinares Brustzentrum Kliniken Essen Mi, Essen, Germany

[10] Brustzentrum Krankenhaus Koln Holweide, Cologne, Germany

[11] Univ Klinikum Erlangen, Erlangen, Germany

[12] Klinikum Zum Roten Kreuz, Munich, Germany

[13] Marien Hosp Witten, Witten, Germany

[14] Campus Charite Mitte, Klin Gynakol, Berlin, Germany

[15] Uniklin Koln, Cologne, Germany

[16] German Breast Grp, Neu Isenburg, Germany

[17] Univ Frauenklin, Rostock, Germany

[18] Univ Klinikum Ulm, Ulm, Germany

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2019年 / 37卷 / 25期

关键词：

PATHOLOGICAL COMPLETE RESPONSE; ALBUMIN-BOUND PACLITAXEL; NEOADJUVANT CHEMOTHERAPY; TRIAL; TRASTUZUMAB; WOMEN; GEPARSIXTO; GEPARSEPTO; ADJUVANT; REGIMENS;

D O I：

10.1200/JCO.18.01842

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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/m(2) (after study amendment, 125 mg/m(2)) or weekly sb-paclitaxel 80 mg/m(2) followed in both arms by four times epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) 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/m(2) compared with NAB-paclitaxel 150 mg/m(2). 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/m(2) compared with NAB-paclitaxel 150 mg/m(2). (C) 2019 by American Society of Clinical Oncology

引用

页码：2226 / +

页数：18

共 30 条

[1] Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100 000 women in 123 randomised trials [J].

Albain, K. ;

Anderson, S. ;

Arriagada, R. ;

Barlow, W. ;

Bergh, J. ;

Bliss, J. ;

Buyse, M. ;

Cameron, D. ;

Carrasco, E. ;

Clarke, M. ;

Correa, C. ;

Coates, A. ;

Collins, R. ;

Costantino, J. ;

Cutter, D. ;

Cuzick, J. ;

Darby, S. ;

Davidson, N. ;

Davies, C. ;

Davies, K. ;

Delmestri, A. ;

Di Leo, A. ;

Dowsett, M. ;

Elphinstone, P. ;

Evans, V. ;

Ewertz, M. ;

Gelber, R. ;

Gettins, L. ;

Geyer, C. ;

Goldhirsch, A. ;

Godwin, J. ;

Gray, R. ;

Gregory, C. ;

Hayes, D. ;

Hill, C. ;

Ingle, J. ;

Jakesz, R. ;

James, S. ;

Kaufmann, M. ;

Kerr, A. ;

MacKinnon, E. ;

McGale, P. ;

McHugh, T. ;

Norton, L. ;

Ohashi, Y. ;

Paik, S. ;

Pan, H. C. ;

Perez, E. ;

Peto, R. ;

Piccart, M. .

LANCET, 2012, 379 (9814) :432-444

[2] Right-Sizing Adjuvant and Neoadjuvant Clinical Trials in Breast Cancer [J].

Berry, Donald A. .

CLINICAL CANCER RESEARCH, 2016, 22 (01) :3-5

[3] Quantification of the completeness of follow-up [J].

Clark, TG ;

Altman, DG ;

De Stavola, BL .

LANCET, 2002, 359 (9314) :1309-1310

[4]

Coombes RC, 2018, CANCER RES, V78

[5] Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis [J].

Cortazar, Patricia ;

Zhang, Lijun ;

Untch, Michael ;

Mehta, Keyur ;

Costantino, Joseph P. ;

Wolmark, Norman ;

Bonnefoi, Herve ;

Cameron, David ;

Gianni, Luca ;

Valagussa, Pinuccia ;

Swain, Sandra M. ;

Prowell, Tatiana ;

Loibl, Sibylle ;

Wickerham, D. Lawrence ;

Bogaerts, Jan ;

Baselga, Jose ;

Perou, Charles ;

Blumenthal, Gideon ;

Blohmer, Jens ;

Mamounas, Eleftherios P. ;

Bergh, Jonas ;

Semiglazov, Vladimir ;

Justice, Robert ;

Eidtmann, Holger ;

Paik, Soonmyung ;

Piccart, Martine ;

Sridhara, Rajeshwari ;

Fasching, Peter A. ;

Slaets, Leen ;

Tang, Shenghui ;

Gerber, Bernd ;

Geyer, Charles E., Jr. ;

Pazdur, Richard ;

Ditsch, Nina ;

Rastogi, Priya ;

Eiermann, Wolfgang ;

von Minckwitz, Gunter .

LANCET, 2014, 384 (9938) :164-172

[6]

European Medicines Agency, EMA949832015

[7]

Furlanetto J, 2017, CANC RES S, V77

[8] Efficacy and safety of nab-paclitaxel 125 mg/m2 and nab-paclitaxel 150 mg/m2 compared to paclitaxel in early high-risk breast cancer. Results from the neoadjuvant randomized GeparSepto study (GBG 69) [J].

Furlanetto, Jenny ;

Jackisch, Christian ;

Untch, Michael ;

Schneeweiss, Andreas ;

Schmatloch, Sabine ;

Aktas, Bahriye ;

Denkert, Carsten ;

Wiebringhaus, Hermann ;

Kuemmel, Sherko ;

Warm, Mathias ;

Paepke, Stefan ;

Just, Marianne ;

Hanusch, Claus ;

Hackmann, John ;

Blohmer, Jens Uwe ;

Clemens, Michael ;

Costa, Serban Dan ;

Gerber, Bernd ;

Nekljudova, Valentina ;

Loibl, Sibylle ;

von Minckwitz, Gunter .

BREAST CANCER RESEARCH AND TREATMENT, 2017, 163 (03) :495-506

[9] Fluorescent CSC models evidence that targeted nanomedicines improve treatment sensitivity of breast and colon cancer stem cells [J].

Gener, Petra ;

Gouveia, Luis Pleno ;

Romero Sabat, Guillem ;

de Sousa Rafael, Diana Fernandes ;

Bergada Fort, Nuria ;

Arranja, Alexandra ;

Fernandez, Yolanda ;

Minana Prieto, Rafael ;

Sayos Ortega, Joan ;

Arango, Diego ;

Abasolo, Ibane ;

Videira, Mafalda ;

Schwartz, Simo, Jr. .

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, 2015, 11 (08) :1883-1892

[10] Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by Anthracycline Regimens in Women With ERBB2/HER2-Negative Breast Cancer-The Evaluating Treatment With Neoadjuvant Abraxane (ETNA) Trial A Randomized Phase 3 Clinical Trial [J].

Gianni, Luca ;

Mansutti, Mauro ;

Anton, Antonio ;

Calvo, Lourdes ;

Bisagni, Giancarlo ;

Bermejo, Begona ;

Semiglazov, Vladimir ;

Thill, Marc ;

Ignacio Chacon, Jose ;

Chan, Arlene ;

Morales, Serafin ;

Alvarez, Isabel ;

Plazaola, Arrate ;

Zambetti, Milvia ;

Redfern, Andrew D. ;

Dittrich, Christian ;

Dent, Rebecca Alexandra ;

Magazzu, Domenico ;

De Fato, Raffaella ;

Valagussa, Pinuccia ;

Tusquets, Ignacio .

JAMA ONCOLOGY, 2018, 4 (03) :302-308

← 1 2 3 →