Your browser doesn't support javascript.
loading
Adaptive Randomization of Neratinib in Early Breast Cancer.
Park, John W; Liu, Minetta C; Yee, Douglas; Yau, Christina; van 't Veer, Laura J; Symmans, W Fraser; Paoloni, Melissa; Perlmutter, Jane; Hylton, Nola M; Hogarth, Michael; DeMichele, Angela; Buxton, Meredith B; Chien, A Jo; Wallace, Anne M; Boughey, Judy C; Haddad, Tufia C; Chui, Stephen Y; Kemmer, Kathleen A; Kaplan, Henry G; Isaacs, Claudine; Nanda, Rita; Tripathy, Debasish; Albain, Kathy S; Edmiston, Kirsten K; Elias, Anthony D; Northfelt, Donald W; Pusztai, Lajos; Moulder, Stacy L; Lang, Julie E; Viscusi, Rebecca K; Euhus, David M; Haley, Barbara B; Khan, Qamar J; Wood, William C; Melisko, Michelle; Schwab, Richard; Helsten, Teresa; Lyandres, Julia; Davis, Sarah E; Hirst, Gillian L; Sanil, Ashish; Esserman, Laura J; Berry, Donald A.
Afiliação
  • Park JW; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Liu MC; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Yee D; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Yau C; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • van 't Veer LJ; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Symmans WF; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Paoloni M; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Perlmutter J; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Hylton NM; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Hogarth M; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • DeMichele A; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Buxton MB; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Chien AJ; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Wallace AM; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Boughey JC; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Haddad TC; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Chui SY; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Kemmer KA; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Kaplan HG; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Isaacs C; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Nanda R; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Tripathy D; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Albain KS; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Edmiston KK; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Elias AD; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Northfelt DW; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Pusztai L; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Moulder SL; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Lang JE; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Viscusi RK; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Euhus DM; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Haley BB; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Khan QJ; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Wood WC; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Melisko M; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Schwab R; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Helsten T; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Lyandres J; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Davis SE; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Hirst GL; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Sanil A; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Esserman LJ; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
  • Berry DA; From University of California, San Francisco (J.W.P., C.Y., L.J.V., N.M.H., M.B.B., A.J.C., M.M., 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.), Univer
N Engl J Med ; 375(1): 11-22, 2016 Jul 07.
Article em En | MEDLINE | ID: mdl-27406346
ABSTRACT

BACKGROUND:

The heterogeneity of breast cancer makes identifying effective therapies challenging. The I-SPY 2 trial, a multicenter, adaptive phase 2 trial of neoadjuvant therapy for high-risk clinical stage II or III breast cancer, evaluated multiple new agents added to standard chemotherapy to assess the effects on rates of pathological complete response (i.e., absence of residual cancer in the breast or lymph nodes at the time of surgery).

METHODS:

We used adaptive randomization to compare standard neoadjuvant chemotherapy plus the tyrosine kinase inhibitor neratinib with control. Eligible women were categorized according to eight biomarker subtypes on the basis of human epidermal growth factor receptor 2 (HER2) status, hormone-receptor status, and risk according to a 70-gene profile. Neratinib was evaluated against control with regard to 10 biomarker signatures (prospectively defined combinations of subtypes). The primary end point was pathological complete response. Volume changes on serial magnetic resonance imaging were used to assess the likelihood of such a response in each patient. Adaptive assignment to experimental groups within each disease subtype was based on Bayesian probabilities of the superiority of the treatment over control. Enrollment in the experimental group was stopped when the 85% Bayesian predictive probability of success in a confirmatory phase 3 trial of neoadjuvant therapy reached a prespecified threshold for any biomarker signature ("graduation"). Enrollment was stopped for futility if the probability fell to below 10% for every biomarker signature.

RESULTS:

Neratinib reached the prespecified efficacy threshold with regard to the HER2-positive, hormone-receptor-negative signature. Among patients with HER2-positive, hormone-receptor-negative cancer, the mean estimated rate of pathological complete response was 56% (95% Bayesian probability interval [PI], 37 to 73%) among 115 patients in the neratinib group, as compared with 33% among 78 controls (95% PI, 11 to 54%). The final predictive probability of success in phase 3 testing was 79%.

CONCLUSIONS:

Neratinib added to standard therapy was highly likely to result in higher rates of pathological complete response than standard chemotherapy with trastuzumab among patients with HER2-positive, hormone-receptor-negative breast cancer. (Funded by QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Quinolinas / Neoplasias da Mama / Protocolos de Quimioterapia Combinada Antineoplásica Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: N Engl J Med Ano de publicação: 2016 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Quinolinas / Neoplasias da Mama / Protocolos de Quimioterapia Combinada Antineoplásica Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: N Engl J Med Ano de publicação: 2016 Tipo de documento: Article