Intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for neoadjuvant treatment of high-risk early breast cancer (GeparOcto-GBG 84): A randomised phase III trial

被引：89

作者：

Schneeweiss, Andreas ^{[1
]}

Moebus, Volker ^{[2
]}

Tesch, Hans ^{[3
]}

Hanusch, Claus ^{[4
]}

Denkert, Carsten ^{[5
]}

Luebbe, Kristina ^{[6
]}

Huober, Jens ^{[7
]}

Klare, Peter ^{[8
]}

Kuemmel, Sherko ^{[9
]}

Untch, Michael ^{[10
]}

Kast, Karin ^{[11
]}

Jackisch, Christian ^{[12
]}

Thomalla, Joerg ^{[13
]}

Ingold-Heppner, Barbara ^{[5
]}

Blohmer, Jens-Uwe ^{[5
]}

Rezai, Mahdi ^{[14
]}

Frank, Matthias ^{[15
]}

Engels, Knut ^{[16
]}

Rhiem, Kerstin ^{[17
]}

Fasching, Peter Andreas ^{[18
]}

Nekljudova, Valentina ^{[19
]}

von Minckwitz, Gunter ^{[19
]}

Loibl, Sibylle ^{[3
,19
]}

机构：

[1] Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[2] Clin Frankfurt Hoechst, Dept Gynaecol & Obstet, Frankfurt, Germany

[3] Praxis Bethanien, Frankfurt, Germany

[4] Clin Red Cross, Munich, Germany

[5] Charite, Berlin, Germany

[6] Henriettenstiftung Hannover, Hannover, Germany

[7] Univ Hosp Ulm, Ulm, Germany

[8] Praxisklin Krebsheilkunde Frauen Berlin, Berlin, Germany

[9] Clin Essen Mitte, Breast Ctr, Essen, Germany

[10] HELIOS Clin Berlin Buch, Berlin, Germany

[11] Univ Hosp Dresden, Dresden, Germany

[12] Sana Clin Offenbach, Offenbach, Germany

[13] Clin Haematol & Oncol Koblenz, Koblenz, Germany

[14] Luisenkrankenhaus Dusseldorf, Med Ctr, Dusseldorf, Germany

[15] Ortenau Clin, Offenburg, Germany

[16] Zentrum Pathol Zytol & Mol Pathol Neuss, Neuss, Germany

[17] Univ Hosp Cologne, Clin Ctr Familial Breast & Ovarian Canc, Cologne, Germany

[18] Friedrich Alexander Univ Erlangen Nuremberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Dept Gynecol & Obstet, Erlangen, Germany

[19] German Breast Grp, Neu Isenburg, Germany

来源：

EUROPEAN JOURNAL OF CANCER | 2019年 / 106卷

关键词：

Dose-dense; Neoadjuvant; High-risk early breast cancer; Carboplatin; PATHOLOGICAL COMPLETE RESPONSE; ADJUVANT CHEMOTHERAPY; TRASTUZUMAB; SURVIVAL; REGIMENS; WOMEN; COMBINATION; GEPARSIXTO; PERTUZUMAB; SCHEDULE;

D O I：

10.1016/j.ejca.2018.10.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: GeparOcto compared efficacy and safety of two chemotherapy regimens in high-risk early breast cancer (BC): sequential treatment with intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly treatment with paclitaxel plus non-pegylated liposomal doxorubicin (M, Myocet (R)) with additional carboplatin (PM(Cb)) in triple-negative BC (TNBC). Patients and methods: Patients with cT1c-cT4a-d and centrally assessed human epidermal growth factor receptor (HER) 2-positive BC or TNBC were eligible, irrespective of nodal status, luminal B-like tumours only if pN+. Patients were randomised (stratified by BC subtype, Ki67, lymphocyte-predominant BC) to receive 18 weeks of E (150 mg/m(2)) followed by P (225 mg/m(2)) followed by C (2000 mg/m(2)), each q2w for 3 cycles or weekly P (80 mg/m(2)) plus M (20 mg/m(2)) plus, in TNBC, Cb (area under curve (AUC) 1.5). HER2-positive BC patients additionally received trastuzumab (6 [loading dose 8]mg/kg q3w) and pertuzumab (420 [840]mg q3w) with all P and C cycles. Primary end-point was pathological complete response (pCR, ypT0/is ypN0), secondary end-points included other pCR definitions, pCR in stratified subpopulations, tolerability and compliance. This trial is registered with ClinicalTrials.gov number NCT02125344. Results: 945/961 randomised patients started treatment. The median age was 48 years; 7.6% had cT3-4, 46% cN+, 66% G3, 40% HER2-positive, 43% TNBC. pCR rate with iddEPC was 48.3%, with PM(Cb) 48.0%, respectively (PM(Cb) versus iddEPC odds ratio 0.99; 95% confidence interval 0.77-1.28, P = 0.979) with no significant differences observed in TNBC, HER2-positive, luminal B-like subtypes. 16.4% with iddEPC and 34.1% with PM(Cb) discontinued treatment (P < 0.001), mainly due to adverse events; two patients on PM(Cb) died. Conclusions: In high-risk early BC there is no difference in pCR rates following neoadjuvant treatment with iddEPC or weekly PM(Cb), respectively. iddEPC is one of the effective dose-dense regimens feasible in daily practice. (C) 2018 Elsevier Ltd. All rights reserved.

引用

页码：181 / 192

页数：12

共 32 条

[1] Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials [J].

Alberro, J. A. ;

Ballester, B. ;

Deulofeu, P. ;

Fabregas, R. ;

Fraile, M. ;

Gubern, J. M. ;

Janer, J. ;

Moral, A. ;

de Pablo, J. L. ;

Penalva, G. ;

Puig, P. ;

Ramos, M. ;

Rojo, R. ;

Santesteban, P. ;

Serra, C. ;

Sola, M. ;

Solarnau, L. ;

Solsona, J. ;

Veloso, E. ;

Vidal, S. ;

Abe, O. ;

Abe, R. ;

Enomoto, K. ;

Kikuchi, K. ;

Koyama, H. ;

Masuda, H. ;

Nomura, Y. ;

Ohashi, Y. ;

Sakai, K. ;

Sugimachi, K. ;

Toi, M. ;

Tominaga, T. ;

Uchino, J. ;

Yoshida, M. ;

Coles, C. E. ;

Haybittle, J. L. ;

Moebus, V. ;

Leonard, C. F. ;

Calais, G. ;

Garaud, P. ;

Collett, V. ;

Davies, C. ;

Delmestri, A. ;

Sayer, J. ;

Harvey, V. J. ;

Holdaway, I. M. ;

Kay, R. G. ;

Mason, B. H. ;

Forbe, J. F. ;

Franci, P. A. .

LANCET ONCOLOGY, 2018, 19 (01) :27-39

[2]

von Minckwitz Gunter, 2017, N Engl J Med, V377, P122, DOI [10.1056/NEJMx170011, 10.1056/NEJMoa1703643]

[3] Breast conservation after neoadjuvant chemotherapy: The M.D. Anderson Cancer Center experience [J].

Chen, AM ;

Meric-Bernstam, F ;

Hunt, KK ;

Thames, HD ;

Oswald, MJ ;

Outlaw, ED ;

Strom, EA ;

McNeese, MD ;

Kuerer, HM ;

Ross, MI ;

Singletary, SE ;

Ames, FC ;

Feig, BW ;

Sahin, AA ;

Perkins, GH ;

Schechter, NR ;

Hortobagyi, GN ;

Buchholz, TA .

JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (12) :2303-2312

[4] Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First report of intergroup trial C9741/cancer and leukemia group B trial 9741 [J].

Citron, ML ;

Berry, DA ;

Cirrincione, C ;

Hudis, C ;

Winer, EP ;

Gradishar, WJ ;

Davidson, NE ;

Martino, S ;

Livingston, R ;

Ingle, JN ;

Perez, EA ;

Carpenter, J ;

Hurd, D ;

Holland, JF ;

Smith, BL ;

Sartor, CI ;

Leung, EH ;

Abrams, J ;

Schilsky, RL ;

Muss, HB ;

Norton, L .

JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (08) :1431-1439

[5]

Clopper CJ, 1934, BIOMETRIKA, V26, P404, DOI 10.2307/2331986

[6]

Cortazar P, 2019, LANCET, V393, P986

[7] Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 x 2 factorial, randomised phase 3 trial [J].

Del Mastro, Lucia y ;

De Placido, Sabino ;

Bruzzi, Paolo ;

De Laurentiis, Michele ;

Boni, Corrado ;

Cavazzini, Giovanna ;

Durando, Antonio ;

Turletti, Anna ;

Nistico, Cecilia ;

Valle, Enrichetta ;

Garrone, Ornella ;

Puglisi, Fabio ;

Montemurro, Filippo ;

Barni, Sandro ;

Ardizzoni, Andrea ;

Gamucci, Teresa ;

Colantuoni, Giuseppe ;

Giuliano, Mario ;

Gravina, Adriano ;

Papaldo, Paola ;

Bighin, Claudia ;

Bisagni, Giancarlo ;

Forestieri, Valeria ;

Cognetti, Francesco .

LANCET, 2015, 385 (9980) :1863-1872

[8] Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy [J].

Denkert, Carsten ;

von Minckwitz, Gunter ;

Darb-Esfahani, Silvia ;

Lederer, Bianca ;

Heppner, Barbara I. ;

Weber, Karsten E. ;

Budczies, Jan ;

Huober, Jens ;

Klauschen, Frederick ;

Furlanetto, Jenny ;

Schmitt, Wolfgang D. ;

Blohmer, Jens-Uwe ;

Karn, Thomas ;

Pfitzner, Berit M. ;

Kuemmel, Sherko ;

Engels, Knut ;

Schneeweiss, Andreas ;

Hartmann, Arndt ;

Noske, Aurelia ;

Fasching, Peter A. ;

Jackisch, Christian ;

van Mackelenbergh, Marion ;

Sinn, Peter ;

Schem, Christian ;

Hanusch, Claus ;

Untch, Michael ;

Loibl, Sibylle .

LANCET ONCOLOGY, 2018, 19 (01) :40-50

[9] Phase 3 study evaluating efficacy and safety of veliparib (V) plus carboplatin (Cb) or Cb in combination with standard neoadjuvant chemotherapy (NAC) in patients (pts) with early stage triple-negative breast cancer (TNBC) [J].

Geyer, Charles E. ;

O'Shaughnessy, Joyce ;

Untch, Michael ;

Sikov, William ;

Rugo, Hope S. ;

McKee, Mark D. ;

Huober, Jens Bodo ;

Golshan, Mehra ;

Giranda, Vincent L. ;

Von Minckwitz, Gunter ;

Maag, David ;

Sullivan, Danielle Marie ;

Wolmark, Norman ;

McIntyre, Kristi ;

Lorenzo, Jose Juan Ponce ;

Filho, Otto Metzger ;

Rastogi, Priya ;

Symmans, William Fraser ;

Liu, Xuan ;

Loibl, Sibylle .

JOURNAL OF CLINICAL ONCOLOGY, 2017, 35

[10] Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial [J].

Gianni, Luca ;

Pienkowski, Tadeusz ;

Im, Young-Hyuck ;

Roman, Laslo ;

Tseng, Ling-Ming ;

Liu, Mei-Ching ;

Lluch, Ana ;

Staroslawska, Elzbieta ;

de la Haba-Rodriguez, Juan ;

Im, Seock-Ah ;

Pedrini, Jose Luiz ;

Poirier, Brigitte ;

Morandi, Paolo ;

Semiglazov, Vladimir ;

Srimuninnimit, Vichien ;

Bianchi, Giulia ;

Szado, Tania ;

Ratnayake, Jayantha ;

Ross, Graham ;

Valagussa, Pinuccia .

LANCET ONCOLOGY, 2012, 13 (01) :25-32

← 1 2 3 4 →