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

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