Abstract | BACKGROUND: METHODS: In this ongoing trial, women are eligible for participation if they have stage II or III breast cancer with a tumor 2.5 cm or larger in diameter; cancers are categorized into eight biomarker subtypes on the basis of status with regard to human epidermal growth factor receptor 2 (HER2), hormone receptors, and a 70-gene assay. Patients undergo adaptive randomization within each biomarker subtype to receive regimens that have better performance than the standard therapy. Regimens are evaluated within 10 biomarker signatures (i.e., prospectively defined combinations of biomarker subtypes). Veliparib- carboplatin plus standard therapy was considered for HER2-negative tumors and was therefore evaluated in 3 signatures. The primary end point is pathological complete response. Tumor volume changes measured by magnetic resonance imaging during treatment are used to predict whether a patient will have a pathological complete response. Regimens move on from phase 2 if and when they have a high Bayesian predictive probability of success in a subsequent phase 3 neoadjuvant trial within the biomarker signature in which they performed well. RESULTS: CONCLUSIONS: The process used in our trial showed that veliparib- carboplatin added to standard therapy resulted in higher rates of pathological complete response than standard therapy alone specifically in triple-negative breast cancer. (Funded by the QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).
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Authors | Hope S Rugo, Olufunmilayo I Olopade, Angela DeMichele, Christina Yau, Laura J van 't Veer, Meredith B Buxton, Michael Hogarth, Nola M Hylton, Melissa Paoloni, Jane Perlmutter, W Fraser Symmans, Douglas Yee, A Jo Chien, Anne M Wallace, Henry G Kaplan, Judy C Boughey, Tufia C Haddad, Kathy S Albain, Minetta C Liu, Claudine Isaacs, Qamar J Khan, Julie E Lang, Rebecca K Viscusi, Lajos Pusztai, Stacy L Moulder, Stephen Y Chui, Kathleen A Kemmer, Anthony D Elias, Kirsten K Edmiston, David M Euhus, Barbara B Haley, Rita Nanda, Donald W Northfelt, Debasish Tripathy, William C Wood, Cheryl Ewing, Richard Schwab, Julia Lyandres, Sarah E Davis, Gillian L Hirst, Ashish Sanil, Donald A Berry, Laura J Esserman, I-SPY 2 Investigators |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 375
Issue 1
Pg. 23-34
(Jul 07 2016)
ISSN: 1533-4406 [Electronic] United States |
PMID | 27406347
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzimidazoles
- Poly(ADP-ribose) Polymerase Inhibitors
- veliparib
- Carboplatin
- Paclitaxel
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Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- Bayes Theorem
- Benzimidazoles
(administration & dosage, adverse effects)
- Carboplatin
(administration & dosage, adverse effects)
- Female
- Humans
- Middle Aged
- Neoadjuvant Therapy
- Paclitaxel
(administration & dosage, adverse effects)
- Poly(ADP-ribose) Polymerase Inhibitors
(administration & dosage, adverse effects)
- Triple Negative Breast Neoplasms
(drug therapy, surgery)
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