Originally published as JCO Early Release 10.1200/JCO.2008.19.6618 on March 16 2009

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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

From the GBG Forschungs GmbH, Neu-Isenburg; Dr.-Horst-Schmidt-Kliniken, Breast Unit, Wiesbaden; University Women's Hospital, Mainz; University Women's Hospital, Kiel; Uni-versity 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.

Corresponding author: Gunter von Minckwitz, MD, PhD, GBG Forschungs GmbH, University of Frankfurt, Schleussnerstr 42, Neu-Isenburg, Germany 63263; 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.

Supported by Roche AG, Germany, and by the University College London Hospitals/University College London (UCLH/UCL) Comprehensive Biomedical Research Centre (R.C.S.).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

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• Continuing Trastuzumab Beyond Progression
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• Trastuzumab Beyond Disease Progression: Case Closed?
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