Phase III randomised trial comparing intense dose-dense chemotherapy to tailored dose-dense chemotherapy in high-risk early breast cancer (GAIN-2)

被引：11

作者：

Moebus, Volker ^{[1
]}

Lueck, Hans-Joachim ^{[2
]}

Ladda, Ekkehart ^{[3
]}

Klare, Peter ^{[4
]}

Schmidt, Marcus ^{[5
]}

Schneeweiss, Andreas ^{[6
]}

Grischke, Eva-Maria ^{[7
]}

Wachsmann, Grischa ^{[8
]}

Forstbauer, Helmut ^{[9
]}

Untch, Michael ^{[10
]}

Marme, Frederik ^{[11
]}

Blohmer, Jens-Uwe ^{[12
]}

Jackisch, Christian ^{[13
]}

Huober, Jens ^{[14
]}

Stickeler, Elmar ^{[15
]}

Reinisch, Mattea ^{[16
]}

Link, Theresa ^{[17
,18
]}

Sinn, Bruno, V ^{[19
]}

Janni, Wolfgang ^{[20
]}

Denkert, Carsten ^{[21
]}

Furlanetto, Jenny ^{[22
]}

Engels, Knut ^{[23
]}

Solbach, Christine ^{[24
]}

Schmatloch, Sabine ^{[25
]}

Rey, Julia ^{[22
]}

Burchardi, Nicole ^{[22
]}

Loibl, Sibylle ^{[22
]}

机构：

[1] Goethe Univ Frankfurt, Dept Med Hematol & Oncol 2, Frankfurt, Germany

[2] Gynecol Oncol Practice, Hannover, Germany

[3] Oncol Practice Neumarkt, Hannover, Germany

[4] MediOnko Inst GbR, Berlin, Germany

[5] Johannes Gutenberg Univ Mainz, Dept Obstet & Gynecol, Univ Med Ctr, Mainz, Germany

[6] Univ Hosp & German Canc Res Ctr, Natl Ctr Tumor Dis, Heidelberg, Germany

[7] Univ Clin Tuebingen, Dept Gynecol & Obstet, Tubingen, Germany

[8] Cty Hosp Boblingen, Boblingen, Germany

[9] Oncol Practice Network, Troisdorf, Germany

[10] HELIOS Klinikum Berlin Buch, Dept Gynaecol & Obstet, Breast Canc & Gynecol Oncol Ctr, Berlin, Germany

[11] Univ Hosp Mannheim, Dept Gynaecol & Obstet, Mannheim, Germany

[12] Breast Ctr Charite Univ Med Berlin, Berlin, Germany

[13] Sana Clin Offenbach, Offenbach, Germany

[14] Univ Ulm, Dept Gynecol, Ulm, Germany

[15] Univ Hosp, Aachen, Germany

[16] Kliniken Essen Mitte, Interdisciplinary Breast Unit, Essen, Germany

[17] Tech Univ Dresden, Med Fac, Dept Gynecol & Obstet, Dresden, Germany

[18] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dresden, Germany

[19] Charite Univ Med Berlin, Inst Pathol, Berlin, Germany

[20] Univ Hosp, Dept Gynecol & Obstet, Ulm, Germany

[21] Inst Pathol Philipps Univ Marburg, Marburg, Germany

[22] German Breast Grp, Neu Isenburg, Germany

[23] Ctr Pathol Cytol & Mol Pathol Neuss, Neuss, Germany

[24] Goethe Univ Frankfurt, Breast Ctr, Frankfurt, Germany

[25] Elisabeth Hosp Kassel, Breast Canc Ctr, Kassel, Germany

来源：

EUROPEAN JOURNAL OF CANCER | 2021年 / 156卷

关键词：

Early breast cancer; Adjuvant chemotherapy; Dose-dense chemotherapy; Randomised trial; ADJUVANT CHEMOTHERAPY; WOMEN; MULTICENTER; SURVIVAL;

D O I：

10.1016/j.ejca.2021.07.033

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: The GAIN-2 trial was designed to identify a superior intense dose dense (idd) strategy for high-risk patients with early breast cancer. Here, we report an interim analysis, at which the predefined futility boundary was crossed. Patients and methods: GAIN-2 was an open-label, randomised, multicentre phase III trial. Two thousand eight hundred and eighty seven patients were randomised 1:1 between three courses each of idd epirubicin (E) 150 mg/m(2), nab-paclitaxel (nP) 330 mg/m(2) and cyclophosphamide (C) 2000 mg/m(2) (iddEnPC) versus four cycles of leucocyte nadir-based tailored and dose-dense EC (dtEC) followed by four cycles of tailored and dose-dense docetaxel (dtD) (dtEC-dtD). Results: The duration of median follow-up was 45.8 (range 0.0-88.3) months. Trial objectives included invasive disease-free survival (iDFS) as the primary end-point. A total of 593 patients received the treatment as neoadjuvant chemotherapy. At the time of futility interim analysis, 414 events for iDFS were reported. Overall, there was no difference in iDFS between iddEnPC and dtEC-dtD with 4-year iDFS rates of 84.3% (95% confidence interval (CI) 82.0-86.4%). Among all predefined subgroups, hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-), lobular cancer and <= 50 years subgroups predicted for better iDFS in the dtEC-dtD arm. Overall, 88.1% of patients completed all treatment in both arms. Haematological toxicity grade 3/4 and grade 3/4 non-haematological adverse events were significantly higher with iddEnPC (iddEnPC 50.8% vs dtEC-dtD 45.1%, P = 0.002), especially arthralgia and peripheral sensory neuropathy. Two treatment-related deaths occurred during dtEC-dtD, corresponding to a low mortality rate of 0.07%. Conclusions: iDFS is equal in both regimens, but tailoring dose-dense chemotherapy improved outcomes in HR+/HER2-, lobular cancer and patients <= 50 years. (C) 2021 Elsevier Ltd. All rights reserved.

引用

页码：138 / 148

页数：11

共 50 条

[31] Prognostic and predictive impact of gene expression in node-positive early breast cancer patients receiving dose-dense versus standard-dose adjuvant chemotherapy
Reinisch, Mattea
Bruzas, Simona
Gluz, Oleg
Ataseven, Beyhan
Schmid, Peter
Cortes, Javier
Blohmer, Jens-Uwe
Shenoy, Satyendra
Dyson, Mark H.
Dittmer-Grabowski, Christine
Chiari, Ouafaa
Harrach, Hakima
Gebauer, Daniel
Traut, Alexander
Kuemmel, Sherko
MOLECULAR ONCOLOGY, 2023, 17 (06) : 1060 - 1075
[32] Dose-Dense Chemotherapy Regimen for Breast Cancer Associated with Significant Decline in Ovarian Reserve
Chamani, Isaac J.
Gannon, Alexandra
Connell, Phillip T.
Bisen, Ajit
Kovanci, Ertug
Sangi-Haghpeykar, Haleh
Woodard, Terri
McKenzie, Laurie J.
JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY, 2024, 13 (03) : 465 - 468
[33] The relevance of macrocytosis induction during neoadjuvant dose-dense chemotherapy in breast cancer patients
Jelavic, Tihana Boraska
Podrug, Mario
Ban, Marija
Lovasic, Ingrid Belac
Curic, Zvonimir
Vrdoljak, Eduard
ANTI-CANCER DRUGS, 2022, 33 (01) : E655 - E661
[34] Efficacy of pegfilgrastim to support neoadjuvant dose-dense epirubicin and cyclophosphamide chemotherapy in breast cancer
Xinguang Wang
Yingjian He
Tianfeng Wang
Yuntao Xie
Jinfeng Li
Tao Ouyang
Zhaoqing Fan
Supportive Care in Cancer, 2019, 27 : 3019 - 3025
[35] Long-Term Efficiency and Toxicity of Adjuvant Dose-Dense Sequential Adriamycin-Paclitaxel-Cyclophosphamide Chemotherapy in High-Risk Breast Cancer
Kelemen, Gyoengyi
Uhercsak, Gabriella
Ormandi, Katalin
Eller, Jozsef
Thurzo, Laszlo
Kahan, Zsuzsanna
ONCOLOGY, 2010, 78 (3-4) : 271 - 273
[36] High rate of extra-haematological toxicity compromises dose-dense sequential adjuvant chemotherapy for breast cancer
Brain, E.
Levy, C.
Serin, D.
Roche, H.
Spielmann, M.
Delva, R.
Veyret, C.
Mauriac, L.
Rios, M.
Martin, A. L.
Jimenez, M.
Asselain, B.
Gauthier, M.
Bonnetain, F.
Fumoleau, P.
BRITISH JOURNAL OF CANCER, 2011, 105 (10) : 1480 - 1486
[37] Dose-dense adjuvant chemotherapy in HER2-positive early breast cancer patients before and after the introduction of trastuzumab: Exploratory analysis of the GIM2 trial
Lambertini, Matteo
Poggio, Francesca
Bruzzone, Marco
Conte, Benedetta
Bighin, Claudia
de Azambuja, Evandro
Giuliano, Mario
De Laurentiis, Michele
Cognetti, Francesco
Fabi, Alessandra
Bisagni, Giancarlo
Durando, Antonio
Turletti, Anna
Urracci, Ylenia
Garrone, Ornella
Puglisi, Fabio
Montemurro, Filippo
Ceppi, Marcello
Del Mastro, Lucia
INTERNATIONAL JOURNAL OF CANCER, 2020, 147 (01) : 160 - 169
[38] HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin-based dose-dense sequential chemotherapy
George Fountzilas
Christos Valavanis
Vassiliki Kotoula
Anastasia G Eleftheraki
Konstantine T Kalogeras
Olympia Tzaida
Anna Batistatou
Ralf Kronenwett
Ralph M Wirtz
Mattheos Bobos
Eleni Timotheadou
Nikolaos Soupos
George Pentheroudakis
Helen Gogas
Dimitrios Vlachodimitropoulos
Genovefa Polychronidou
Gerasimos Aravantinos
Angelos Koutras
Christos Christodoulou
Dimitrios Pectasides
Petroula Arapantoni
Journal of Translational Medicine, 10
[39] HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin-based dose-dense sequential chemotherapy
Fountzilas, George
Valavanis, Christos
Kotoula, Vassiliki
Eleftheraki, Anastasia G.
Kalogeras, Konstantine T.
Tzaida, Olympia
Batistatou, Anna
Kronenwett, Ralf
Wirtz, Ralph M.
Bobos, Mattheos
Timotheadou, Eleni
Soupos, Nikolaos
Pentheroudakis, George
Gogas, Helen
Vlachodimitropoulos, Dimitrios
Polychronidou, Genovefa
Aravantinos, Gerasimos
Koutras, Angelos
Christodoulou, Christos
Pectasides, Dimitrios
Arapantoni, Petroula
JOURNAL OF TRANSLATIONAL MEDICINE, 2012, 10
[40] Adjuvant dose-dense chemotherapy in breast cancer: a systematic review and meta-analysis of randomized trials
Fausto Petrelli
Mary Cabiddu
Andrea Coinu
Karen Borgonovo
Mara Ghilardi
Veronica Lonati
Sandro Barni
Breast Cancer Research and Treatment, 2015, 151 : 251 - 259

← 1 2 3 4 5 →