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Clinical Trial
. 2020 Oct 23;22(1):111.
doi: 10.1186/s13058-020-01348-w.

Gemcitabine as adjuvant chemotherapy in patients with high-risk early breast cancer-results from the randomized phase III SUCCESS-A trial

Amelie de Gregorio  1 , Lothar Häberle  2   3 , Peter A Fasching  2 , Volkmar Müller  4 , Iris Schrader  5 , Ralf Lorenz  6 , Helmut Forstbauer  7 , Thomas W P Friedl  8 , Emanuel Bauer  8 , Nikolaus de Gregorio  8 , Miriam Deniz  8 , Visnja Fink  8 , Inga Bekes  8 , Ulrich Andergassen  9 , Andreas Schneeweiss  10 , Hans Tesch  11 , Sven Mahner  9 , Sara Y Brucker  12 , Jens-Uwe Blohmer  13 , Tanja N Fehm  14 , Georg Heinrich  15 , Krisztian Lato  8 , Matthias W Beckmann  2 , Brigitte Rack  8 , Wolfgang Janni  8
Affiliations
Clinical Trial

Gemcitabine as adjuvant chemotherapy in patients with high-risk early breast cancer-results from the randomized phase III SUCCESS-A trial

Amelie de Gregorio et al. Breast Cancer Res. .

Abstract

Background: When chemotherapy is indicated in patients with early breast cancer, regimens that contain anthracyclines and taxanes are established standard treatments. Gemcitabine has shown promising effects on the response and prognosis in patients with metastatic breast cancer. The SUCCESS-A trial (NCT02181101) examined the addition of gemcitabine to a standard chemotherapy regimen in high-risk early breast cancer patients.

Methods: A total of 3754 patients with at least one of the following characteristics were randomly assigned to one of the two treatment arms: nodal positivity, tumor grade 3, age ≤ 35 years, tumor larger than 2 cm, or negative hormone receptor status. The treatment arms received either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide, followed by three cycles of docetaxel (FEC → Doc); or three cycles of FEC followed by three cycles of docetaxel and gemcitabine (FEC → Doc/Gem). The primary study aim was disease-free survival (DFS), and the main secondary objectives were overall survival (OS) and safety.

Results: No differences were observed in the 5-year DFS or OS between FEC → Doc and FEC → Doc/Gem. The hazard ratio was 0.93 (95% CI, 0.78 to 1.12; P = 0.47) for DFS and 0.94 (95% CI, 0.74 to 1.19; P = 0.60) for OS. For patients treated with FEC → Doc and FEC → Doc/Gem, the 5-year probabilities of DFS were 86.6% and 87.2%, and the 5-year probabilities of OS were 92.8% and 92.5%, respectively.

Conclusion: Adding gemcitabine to a standard chemotherapy does not improve the outcomes in patients with high-risk early breast cancer and should therefore not be included in the adjuvant treatment setting.

Trial registration: Clinicaltrials.gov NCT02181101 and EU Clinical Trials Register EudraCT 2005-000490-21. Registered September 2005.

Keywords: Chemotherapy; Early breast cancer; Gemcitabine.

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Conflict of interest statement

AdG: honoraria from Novartis, Roche, Pfizer, Daiichi-Sankyo, Tesaro, and Eisai. PF: honoraria and/or grants from Novartis, Amgen, Pfizer, Eisai, Celgene, Myelo Therapeutics, Merk Sharp & Dohme, Macrogenics, Roche, MSD, Daiichi-Sankyo, TEVA, AstraZeneca, Novartis, Puma, Biontech, Daiichi-Sankyo, and Cepheid. VM: speaker honoraria from Amgen, Astra Zeneca, Celgene, Daiichi-Sankyo, Eisai, Pfizer, Novartis, Roche, Teva, and consultancy honoraria from Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Tesaro, and Nektar. Institutional research support from Novartis, Roche, Seattle Genetics, and Genentech. HF: honoraria from Novartis, Roche, Celgene, Astellas Pharma, and Merck. TWPF: honoraria from Novartis. NdG: honoraria from Roche, Tesaro, Amgen, PharmaMar, Astrazeneca, and Clovis. AS: honoraria, grants, personal fees, and non-financial support from Roche, Celgene, AbbVie, Molecular Partner, AstraZeneca, Pfizer, Novartis, MSD, Tesaro, and Lilly. HT: honoraria from Novartis and Roche. SM: research support, honoraria, travel expenses from AstraZeneca, Bayer, Boehringer Ingelheim, Clovis, Eisai, GlaxoSmithKline, Jenapharm, Janssen-Cilag, Medac, MSD, PharmaMar, Roche, Sensor Kinesis, Teva, and Tesaro. JUB: honoraria from Roche, Novartis, and Pfizer. SYB: honoraria from Novartis, Roche, and Pfizer. MWB: MWB’s institution conducts research with funding from Novartis and Pfizer. BR: honoraria from AstraZeneca, Chugai, Lilly, Novartis, Sanofi-Aventis, and Jannssen-Cilag. WJ: honoraria from Sanofi-Aventis, Novartis, and Pfizer. All other authors have no conflict of interest.

Figures

Fig. 1
Fig. 1
Patient flow chart (Consolidated Standards of Reporting Trials/CONSORT diagram)
Fig. 2
Fig. 2
Kaplan–Meier curves for a disease-free survival relative to treatment arm and Kaplan–Meier curves for b overall survival relative to treatment arm
Fig. 3
Fig. 3
Hazard ratios for the treatment arm (FEC → Doc/Gem versus FEC → Doc) in various subgroups relative to disease-free survival (a) and overall survival (b). Although there was some variation in the estimate of the treatment effect of FEC → Doc/Gem, the P values in the global likelihood ratio tests were nonsignificant. Continuous predictors were evaluated at the first decile (“low”), at the median, and at the ninth decile (“high”)
See this image and copyright information in PMC

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