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Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer.
Rugo, Hope S; Olopade, Olufunmilayo I; DeMichele, Angela; Yau, Christina; van 't Veer, Laura J; Buxton, Meredith B; Hogarth, Michael; Hylton, Nola M; Paoloni, Melissa; Perlmutter, Jane; Symmans, W Fraser; Yee, Douglas; Chien, A Jo; Wallace, Anne M; Kaplan, Henry G; Boughey, Judy C; Haddad, Tufia C; Albain, Kathy S; Liu, Minetta C; Isaacs, Claudine; Khan, Qamar J; Lang, Julie E; Viscusi, Rebecca K; Pusztai, Lajos; Moulder, Stacy L; Chui, Stephen Y; Kemmer, Kathleen A; Elias, Anthony D; Edmiston, Kirsten K; Euhus, David M; Haley, Barbara B; Nanda, Rita; Northfelt, Donald W; Tripathy, Debasish; Wood, William C; Ewing, Cheryl; Schwab, Richard; Lyandres, Julia; Davis, Sarah E; Hirst, Gillian L; Sanil, Ashish; Berry, Donald A; Esserman, Laura J.
Afiliación
  • Rugo HS; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Olopade OI; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • DeMichele A; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Yau C; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • van 't Veer LJ; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Buxton MB; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Hogarth M; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Hylton NM; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Paoloni M; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Perlmutter J; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Symmans WF; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Yee D; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Chien AJ; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Wallace AM; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Kaplan HG; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Boughey JC; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Haddad TC; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Albain KS; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Liu MC; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Isaacs C; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Khan QJ; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Lang JE; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Viscusi RK; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Pusztai L; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Moulder SL; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Chui SY; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Kemmer KA; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Elias AD; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Edmiston KK; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Euhus DM; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Haley BB; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Nanda R; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Northfelt DW; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Tripathy D; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Wood WC; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Ewing C; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Schwab R; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Lyandres J; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Davis SE; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Hirst GL; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Sanil A; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Berry DA; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
  • Esserman LJ; From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.),
N Engl J Med ; 375(1): 23-34, 2016 Jul 07.
Article en En | MEDLINE | ID: mdl-27406347
BACKGROUND: The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin. 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: With regard to triple-negative breast cancer, veliparib-carboplatin had an 88% predicted probability of success in a phase 3 trial. A total of 72 patients were randomly assigned to receive veliparib-carboplatin, and 44 patients were concurrently assigned to receive control therapy; at the completion of chemotherapy, the estimated rates of pathological complete response in the triple-negative population were 51% (95% Bayesian probability interval [PI], 36 to 66%) in the veliparib-carboplatin group versus 26% (95% PI, 9 to 43%) in the control group. The toxicity of veliparib-carboplatin was greater than that of the control. 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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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Bencimidazoles / Protocolos de Quimioterapia Combinada Antineoplásica / Carboplatino / Neoplasias de la Mama Triple Negativas Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: N Engl J Med Año: 2016 Tipo del documento: Article
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Bencimidazoles / Protocolos de Quimioterapia Combinada Antineoplásica / Carboplatino / Neoplasias de la Mama Triple Negativas Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: N Engl J Med Año: 2016 Tipo del documento: Article