Randomized phase II study of the anti-epidermal growth factor receptor monoclonal antibody cetuximab with cisplatin versus cisplatin alone in patients with metastatic triple-negative breast cancer.
Wardley, Andrew M
Ciruelos Gil, E
AffiliationJosé Baselga, Memorial Sloan-Kettering Cancer Center, New York, NY; Patricia Gómez, Vall D'Hebron Institute of Oncology, Barcelona; Miguel A. Climent, Instituto Valenciano de Oncologia, Valencia; Eva Maria Ciruelos Gil, Hospital Universitario 12 de Octubre, Madrid, Spain; Richard Greil, Paracelsus Medical University Salzburg, Salzburg, Austria; Sofia Braga, Instituto Português de Oncologia de Lisboa, Lisbon; António Pêgo, Instituto Português de Oncologia de Coimbra Francisco Gentil E.P.E., Coimbra, Portugal; Andrew M. Wardley, The Christie NHS Foundation Trust, Manchester, United Kingdom; Bella Kaufman, Sheba Medical Center, Tel Hashomer; Salomon M. Stemmer, Davidoff Center, Petach Tiqva, Israel; Arlene Chan, Mount Hospital Perth, Perth, Australia; Jean-Charles Goeminne, Clinique et Maternité Sainte Elisabeth, Namur; Marie-Pascale Graas, Clinique St-Joseph, Liège; Ahmad Awada, Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; M. John Kennedy, Trinity College and St James' Hospital, Dublin, Ireland; Andreas Schneeweiss, National Center for Tumor Diseases, University Hospital, Heidelberg; Angela Zubel, Jutta Groos, Helena Melezínková, Merck KGaA, Darmstadt, Germany.
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AbstractPURPOSEEpidermal growth factor receptor is overexpressed in metastatic triple-negative breast cancers (mTNBCs), an aggressive subtype of breast cancer. Our randomized phase II study investigated cisplatin with or without cetuximab in this setting. PATIENTS AND METHODSPatients who had received no more than one previous chemotherapy regimen were randomly assigned on a 2:1 schedule to receive no more than six cycles of cisplatin plus cetuximab or cisplatin alone. Patients receiving cisplatin alone could switch to cisplatin plus cetuximab or cetuximab alone on disease progression. The primary end point was overall response rate (ORR). Secondary end points studied included progression-free survival (PFS), overall survival (OS), and safety profiles. Analyses included a significance level of α = .10 with no adjustments for multiplicity.ResultsThe full analysis set comprised 115 patients receiving cisplatin plus cetuximab and 58 receiving cisplatin alone; 31 patients whose disease progressed on cisplatin alone switched to cetuximab-containing therapy. The ORR was 20% (95% CI, 13 to 29) with cisplatin plus cetuximab and 10% (95% CI, 4 to 21) with cisplatin alone (odds ratio, 2.13; 95% CI, 0.81 to 5.59; P = .11). Cisplatin plus cetuximab resulted in longer PFS compared with cisplatin alone (median, 3.7 v 1.5 months; hazard ratio [HR], 0.67; 95% CI, 0.47 to 0.97; P = .032). Corresponding median OS was 12.9 versus 9.4 months (HR, 0.82; 95% CI, 0.56 to 1.20; P = .31). Common grade 3/4 adverse events included acne-like rash, neutropenia, and fatigue. CONCLUSIONWhile the primary study end point was not met, adding cetuximab to cisplatin doubled the ORR and appeared to prolong PFS and OS, warranting further investigation in mTNBC.
CitationRandomized phase II study of the anti-epidermal growth factor receptor monoclonal antibody cetuximab with cisplatin versus cisplatin alone in patients with metastatic triple-negative breast cancer. 2013: J Clin Oncol
JournalJournal of Clinical Oncology
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