JCO Early Release, published online ahead of print Mar 16 2009
Journal of Clinical Oncology, 10.1200/JCO.2008.19.6618
Received August 15, 2008
Accepted December 9, 2008
Trastuzumab Beyond Progression in Human Epidermal Growth Factor Receptor 2–Positive Advanced Breast Cancer: A German Breast Group 26/Breast International Group 03-05 Study
Gunter von Minckwitz,* Andreas du Bois, Marcus Schmidt, Nicolai Maass, Tanja Cufer, Felix E. de Jongh, Eduard Maartense, Christoph Zielinski, Manfred Kaufmann, Wolfgang Bauer, Klaus H. Baumann, Michael R. Clemens, Ralph Duerr, Christoph Uleer, Michael Andersson, Robert C. Stein, Valentina Nekljudova, and Sibylle Loibl
From the GBG Forschungs GmbH, Neu-Isenburg; Dr.-Horst-Schmidt-Kliniken, Breast Unit, Wiesbaden; University Women's Hospital, Mainz; University Women's Hospital, Kiel; University Women's Hospital, Frankfurt/Main; Schwarzwald-Baar Klinikum, Villingen-Schwenningen; University Women's Hospital, Marburg; Klinikum Mutterhaus der Borromaeerinnen, Trier; Klinikum Deggendorf; and Gemeinschaftspraxis Papcke/Uleer, Hildesheim, Germany; Institute of Oncology, Ljubljana, Slovenia; Ikazia Ziekenhuis, Rotterdam; and Reinier de Graaf Gasthuis, Delft, the Netherlands; Clinical Division of Oncology, Department of Medicine I, Medical University Vienna and Central European Cooperative Oncology Group, Vienna, Austria; Rigshospitalet University Hospital, Copenhagen, Denmark; and University College London Hospitals, London, United Kingdom.
* To whom correspondence should be addressed. E-mail: Gunter.vonMinckwitz{at}germanbreastgroup.de
Purpose: Trastuzumab shows clinical activity in human epidermal growth factor receptor 2 (HER-2)–positive early and advanced breast cancer. In the German Breast Group 26/Breast International Group 03-05 trial, we investigated if trastuzumab treatment should be continued beyond progression.
Methods: Patients with HER-2–positive breast cancer that progresses during treatment with trastuzumab were randomly assigned to receive capecitabine (2,500 mg/m2 body-surface area on days 1 through 14 [1,250 mg/m2 semi-daily]) alone or with continuation of trastuzumab (6 mg/kg body weight) in 3-week cycles. The primary end point was time to progression.
Results: We randomly assigned 78 patients to capecitabine and 78 patients to capecitabine plus trastuzumab. Sixty-five events and 38 deaths in the capecitabine group and 62 events and 33 deaths in the capecitabine-plus-trastuzumab group occurred during 15.6 months of follow-up. Median times to progression were 5.6 months in the capecitabine group and 8.2 months in the capecitabine-plus-trastuzumab group with an unadjusted hazard ratio of 0.69 (95% CI, 0.48 to 0.97; two-sided log-rank P = .0338). Overall survival rates were 20.4 months (95% CI, 17.8 to 24.7) in the capecitabine group and 25.5 months (95% CI, 19.0 to 30.7) in the capecitabine-plus-trastuzumab group (P = .257). Overall response rates were 27.0% with capecitabine and 48.1% with capecitabine plus trastuzumab (odds ratio, 2.50; P = .0115). Continuation of trastuzumab beyond progression was not associated with increased toxicity.
Conclusion: Continuation of trastuzumab plus capecitabine showed a significant improvement in overall response and time to progression compared with capecitabine alone in women with HER-2–positive breast cancer who experienced progression during trastuzumab treatment.
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