Trastuzumab beyond progression: Overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer

• Published in: European journal of cancer (1990) Vol. 47; no. 15; pp. 2273 - 2281
• Main Authors: von Minckwitz, Gunter, Schwedler, Kathrin, Schmidt, Marcus, Barinoff, Jana, Mundhenke, Christoph, Cufer, Tanja, Maartense, Eduard, de Jongh, Felix E, Baumann, Klaus H, Bischoff, Joachim, Harbeck, Nadia, Lück, Hans-Joachim, Maass, Nicolai, Zielinski, Christoph, Andersson, Michael, Stein, Robert C, Nekljudova, Valentina, Loibl, Sibylle
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-10-2011; Elsevier
• Subjects: Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - enzymology; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Capecitabine; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Disease-Free Survival; Europe; Female; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Hematology, Oncology and Palliative Medicine; Humans; Kaplan-Meier Estimate; Medical sciences; Metastatic breast cancer; Molecular Targeted Therapy; Pharmacology. Drug treatments; Progression; Proportional Hazards Models; Prospective Studies; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - metabolism; Risk Assessment; Risk Factors; Survival; Survival Rate; Time Factors; Trastuzumab; Treatment Outcome; Tumors; Europe; Progression; Metastatic breast cancer; Survival; Trastuzumab; Antineoplastic agent; Phase III trial; Breast disease; erbB2 Gene; Breast cancer; Monoclonal antibody; Malignant tumor; Metastasis; Human Epidermal growth factor Receptor 2; Mammary gland diseases; Cancerology; Treatment; C-Onc gene; Advanced stage; Protooncogene; Cancer
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2011.06.021

Abstract Background Continuation of trastuzumab plus capecitabine (XH) showed a significantly improved overall response rate and time to progression compared with capecitabine (X) alone in women with HER2-positive breast cancer progressing during trastuzumab treatment. Here, we report the final analysis on overall survival. Patients and methods Patients with HER2-positive, advanced breast cancer who progressed during treatment with trastuzumab with or without 1st-line metastatic chemotherapy were prospectively randomised to X (2500 mg/m2 on days 1–14, q3w) or XH (6 (8) mg/kg, q3w). Overall survival was a pre-specified secondary end-point. Results Median follow-up at June 2010 was 20.7 months. Fifty nine of 74 and 60 of 77 patients died in the X and XH arm, respectively. Median overall survival was 20.6 and 24.9 months with X and XH, respectively (HR = 0.94 [0.65–1.35]; p = 0.73). Performance status and metastatic site were independent prognosticators for overall survival. No difference between treatment arms was observed for patients who achieved clinical response or clinical benefit, respectively. Patients who continued/restarted anti-HER2 treatment (trastuzumab or lapatinib) after 2nd progression ( N = 52) had a post-progression survival of 18.8 compared with 13.3 months for those who did not receive 3rd line treatment with anti-HER2 agents ( N = 88) (HR 0.63; p = 0.02). Conclusions Final overall survival analysis of the GBG-26 study did not demonstrate a significant survival benefit for treatment beyond progression with trastuzumab. However, in a post-hoc analysis, patients receiving anti-HER2 treatment as 3rd line therapy showed a better post-progression survival than those not receiving this targeted treatment.