• Gunter von Minckwitz, Marion Procter, Evandro de Azambuja, Dimitrios Zardavas, Mark Benyunes, Giuseppe Viale, Thomas Suter, Amal Arahmani, Nathalie Rouchet, Emma Clark, Adam Knott, Istvan Lang, Christelle Levy, Denise A Yardley, Jose Bines, Richard D Gelber, Martine Piccart, Jose Baselga, and APHINITY Steering Committee and Investigators.
• From the German Breast Group, Neu-Isenburg, Germany (G.M.); Frontier Science (Scotland), Kincraig, United Kingdom (M. Procter); the Breast European Adjuvant Study Team (BrEAST) Data Center (E.A., N.R.), the Breast International Group (D.Z., A.A.), and Institut Jules Bordet, Université Libre de Bruxelles (M. Piccart) - all in Brussels; Roche Pharma (M.B., E.C., A.K.) and the Department of Cardiology, Cardio-Oncology, Bern University Hospital (T.S.) - both in Bern, Switzerland; the Department of Pathology, European Institute of Oncology, University of Milan, Milan (G.V.); the National Institute of Oncology, Budapest, Hungary (I.L.); Centre François Baclesse, Caen, France (C.L.); the Sarah Cannon Research Institute and Tennessee Oncology, Nashville (D.A.Y.); Instituto Nacional de Câncer, Rio de Janeiro (J. Bines); Dana-Farber Cancer Institute, Harvard Medical School, Harvard T. H. Chan School of Public Health, and Frontier Science and Technology Research Foundation - all in Boston (R.D.G.); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (J. Baselga).
• N. Engl. J. Med. 2017 Jul 13; 377 (2): 122131122-131.

BackgroundPertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer.MethodsWe randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease-free survival rate of 91.8% with pertuzumab and 89.2% with placebo.ResultsIn the trial population, 63% of the patients who were randomly assigned to receive pertuzumab (2400 patients) or placebo (2405 patients) had node-positive disease and 36% had hormone-receptor-negative disease. Disease recurrence occurred in 171 patients (7.1%) in the pertuzumab group and 210 patients (8.7%) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.66 to 1.00; P=0.045). The estimates of the 3-year rates of invasive-disease-free survival were 94.1% in the pertuzumab group and 93.2% in the placebo group. In the cohort of patients with node-positive disease, the 3-year rate of invasive-disease-free survival was 92.0% in the pertuzumab group, as compared with 90.2% in the placebo group (hazard ratio for an invasive-disease event, 0.77; 95% CI, 0.62 to 0.96; P=0.02). In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease-free survival was 97.5% in the pertuzumab group and 98.4% in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95% CI, 0.68 to 1.86; P=0.64). Heart failure, cardiac death, and cardiac dysfunction were infrequent in both treatment groups. Diarrhea of grade 3 or higher occurred almost exclusively during chemotherapy and was more frequent with pertuzumab than with placebo (9.8% vs. 3.7%).ConclusionsPertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to trastuzumab and chemotherapy. Diarrhea was more common with pertuzumab than with placebo. (Funded by F. Hoffmann-La Roche/Genentech; APHINITY ClinicalTrials.gov number, NCT01358877 .).

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