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Datopotamab-deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial.
Khoury, Katia; Meisel, Jane L; Yau, Christina; Rugo, Hope S; Nanda, Rita; Davidian, Marie; Tsiatis, Butch; Chien, A Jo; Wallace, Anne M; Arora, Mili; Rozenblit, Mariya; Hershman, Dawn L; Zimmer, Alexandra; Clark, Amy S; Beckwith, Heather; Elias, Anthony D; Stringer-Reasor, Erica; Boughey, Judy C; Nangia, Chaitali; Vaklavas, Christos; Omene, Coral; Albain, Kathy S; Kalinsky, Kevin M; Isaacs, Claudine; Tseng, Jennifer; Roussos Torres, Evanthia T; Thomas, Brittani; Thomas, Alexandra; Sanford, Amy; Balassanian, Ronald; Ewing, Cheryl; Yeung, Kay; Sauder, Candice; Sanft, Tara; Pusztai, Lajos; Trivedi, Meghna S; Outhaythip, Ashton; Li, Wen; Onishi, Natsuko; Asare, Adam L; Beineke, Philip; Norwood, Peter; Brown-Swigart, Lamorna; Hirst, Gillian L; Matthews, Jeffrey B; Moore, Brian; Fraser Symmans, W; Price, Elissa; Beedle, Carolyn; Perlmutter, Jane.
Afiliação
  • Khoury K; University of Alabama at Birmingham, Birmingham, AL, USA.
  • Meisel JL; Emory University, Atlanta, GA, USA.
  • Yau C; University of California San Francisco, San Francisco, CA, USA.
  • Rugo HS; University of California San Francisco, San Francisco, CA, USA.
  • Nanda R; University of Chicago, Chicago, IL, USA.
  • Davidian M; North Carolina State University, Raleigh, NC, USA.
  • Tsiatis B; North Carolina State University, Raleigh, NC, USA.
  • Chien AJ; University of California San Francisco, San Francisco, CA, USA.
  • Wallace AM; University of California San Diego, San Diego, CA, USA.
  • Arora M; University of California Davis, Davis, CA, USA.
  • Rozenblit M; Yale University, New Haven, CT, USA.
  • Hershman DL; Columbia University, New York, NY, USA.
  • Zimmer A; Oregon Health Sciences University, Portland, OR, USA.
  • Clark AS; University of Pennsylvania, Philadelphia, PA, USA.
  • Beckwith H; University of Minnesota, Minneapolis, MN, USA.
  • Elias AD; University of Colorado Denver, Denver, CO, USA.
  • Stringer-Reasor E; University of Alabama at Birmingham, Birmingham, AL, USA.
  • Boughey JC; The Mayo Clinic, Rochester, MN, USA.
  • Nangia C; HOAG Family Cancer Institute, Newport Beach, CA, USA.
  • Vaklavas C; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
  • Omene C; Cooperman Barnabas Medical Center, New Brunswick, NJ, USA.
  • Albain KS; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
  • Kalinsky KM; Stritch School of Medicine, Loyola University Chicago, Chicago, IL, USA.
  • Isaacs C; Emory University, Atlanta, GA, USA.
  • Tseng J; Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.
  • Roussos Torres ET; City of Hope Orange County Lennar Foundation Cancer Center, Orange County, CA, USA.
  • Thomas B; University of Southern California, Los Angeles, CA, USA.
  • Thomas A; Sparrow Health System, Lansing, MI, USA.
  • Sanford A; Wake Forest University, Winston-Salem, NC, USA.
  • Balassanian R; Sanford Health, Sioux Falls, SD, USA.
  • Ewing C; University of California San Francisco, San Francisco, CA, USA.
  • Yeung K; University of California San Francisco, San Francisco, CA, USA.
  • Sauder C; University of California San Diego, San Diego, CA, USA.
  • Sanft T; University of California Davis, Davis, CA, USA.
  • Pusztai L; Yale University, New Haven, CT, USA.
  • Trivedi MS; Yale University, New Haven, CT, USA.
  • Outhaythip A; Columbia University, New York, NY, USA.
  • Li W; Oregon Health Sciences University, Portland, OR, USA.
  • Onishi N; University of California San Francisco, San Francisco, CA, USA.
  • Asare AL; University of California San Francisco, San Francisco, CA, USA.
  • Beineke P; University of California San Francisco, San Francisco, CA, USA.
  • Norwood P; Quantum Leap Healthcare Collaborative, San Francisco, CA, USA.
  • Brown-Swigart L; Quantum Leap Healthcare Collaborative, San Francisco, CA, USA.
  • Hirst GL; Quantum Leap Healthcare Collaborative, San Francisco, CA, USA.
  • Matthews JB; University of California San Francisco, San Francisco, CA, USA.
  • Moore B; University of California San Francisco, San Francisco, CA, USA.
  • Fraser Symmans W; University of California San Francisco, San Francisco, CA, USA.
  • Price E; Wake Forest University, Winston-Salem, NC, USA.
  • Beedle C; University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Perlmutter J; University of California San Francisco, San Francisco, CA, USA.
Nat Med ; 2024 Sep 14.
Article em En | MEDLINE | ID: mdl-39277671
ABSTRACT
Among the goals of patient-centric care are the advancement of effective personalized treatment, while minimizing toxicity. The phase 2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimizing individual outcomes. Here we tested datopotamab-deruxtecan (Dato-DXd) in the I-SPY2.2 trial for patients with high-risk stage 2/3 breast cancer. I-SPY2.2 uses a sequential multiple assignment randomization trial design that includes three sequential blocks of biologically targeted neoadjuvant treatment the experimental agent(s) (block A), a taxane-based regimen tailored to the tumor subtype (block B) and doxorubicin-cyclophosphamide (block C). Patients are randomized into arms consisting of different investigational block A treatments. Algorithms based on magnetic resonance imaging and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathological complete response, the primary endpoint. There are two primary efficacy analyses after block A and across all blocks for the six prespecified breast cancer subtypes (defined by clinical hormone receptor/human epidermal growth factor receptor 2 (HER2) status and/or the response-predictive subtypes). We report results of 103 patients treated with Dato-DXd. While Dato-DXd did not meet the prespecified threshold for success (graduation) after block A in any subtype, the treatment strategy across all blocks graduated in the hormone receptor-negative HER2-Immune-DNA repair deficiency- subtype with an estimated pathological complete response rate of 41%. No new toxicities were observed, with stomatitis and ocular events occurring at low grades. Dato-DXd was particularly active in the hormone receptor-negative/HER2-Immune-DNA repair deficiency- signature, warranting further investigation, and was safe in other subtypes in patients who followed the treatment strategy. ClinicalTrials.gov registration NCT01042379 .
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Nat Med Assunto da revista: BIOLOGIA MOLECULAR / MEDICINA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Nat Med Assunto da revista: BIOLOGIA MOLECULAR / MEDICINA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos