Pathologic and molecular responses to neoadjuvant trastuzumab and/or lapatinib from a phase II randomized trial in HER2-positive breast cancer (TRIO-US B07)
| Autor: | Judy Dering, Linda D. Bosserman, Alejandra T. Perez, Christina Curtis, Jason J. Zoeller, Sara A. Hurvitz, Dennis J. Slamon, Ravindranath Patel, Gregory R. Bean, April Kennedy, Katherine McNamara, B DiCarlo, R Dichmann, Aruna Mani, Armando E. Giuliano, Eran Kotler, Joan S. Brugge, Carmen Calfa, Michael F. Press, Heather Allen, Hsiao Wang Chen, David Molthrop, Jennifer L. Caswell-Jin, Brad Adams, Lee Zehngebot |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Receptor ErbB-2 medicine.medical_treatment General Physics and Astronomy law.invention Breast cancer 0302 clinical medicine ErbB-2 Randomized controlled trial law Trastuzumab Antineoplastic Combined Chemotherapy Protocols Tumor Microenvironment Molecular Targeted Therapy lcsh:Science skin and connective tissue diseases Neoadjuvant therapy Cancer education.field_of_study Multidisciplinary Combination chemotherapy Middle Aged Neoadjuvant Therapy Gene Expression Regulation Neoplastic Treatment Outcome 6.1 Pharmaceuticals 030220 oncology & carcinogenesis Female medicine.drug Receptor medicine.medical_specialty Stromal cell Science Clinical Trials and Supportive Activities Population Breast Neoplasms Lapatinib Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Targeted therapies Immune system Clinical Research Internal medicine Breast Cancer medicine Humans education neoplasms Aged Neoplastic business.industry Evaluation of treatments and therapeutic interventions General Chemistry medicine.disease Clinical trial 030104 developmental biology Gene Expression Regulation lcsh:Q business Hormone |
| Zdroj: | Nature communications, vol 11, iss 1 Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) Nature Communications |
| Popis: | In this multicenter, open-label, randomized phase II investigator-sponsored neoadjuvant trial with funding provided by Sanofi and GlaxoSmithKline (TRIO-US B07, Clinical Trials NCT00769470), participants with early-stage HER2-positive breast cancer (N = 128) were recruited from 13 United States oncology centers throughout the Translational Research in Oncology network. Participants were randomized to receive trastuzumab (T; N = 34), lapatinib (L; N = 36), or both (TL; N = 58) as HER2-targeted therapy, with each participant given one cycle of this designated anti-HER2 therapy alone followed by six cycles of standard combination chemotherapy with the same anti-HER2 therapy. The primary objective was to estimate the rate of pathologic complete response (pCR) at the time of surgery in each of the three arms. In the intent-to-treat population, we observed similar pCR rates between T (47%, 95% confidence interval [CI] 30–65%) and TL (52%, 95% CI 38–65%), and a lower pCR rate with L (25%, 95% CI 13–43%). In the T arm, 100% of participants completed all protocol-specified treatment prior to surgery, as compared to 69% in the L arm and 74% in the TL arm. Tumor or tumor bed tissue was collected whenever possible pre-treatment (N = 110), after one cycle of HER2-targeted therapy alone (N = 89), and at time of surgery (N = 59). Higher-level amplification of HER2 and hormone receptor (HR)-negative status were associated with a higher pCR rate. Large shifts in the tumor, immune, and stromal gene expression occurred after one cycle of HER2-targeted therapy. In contrast to pCR rates, the L-containing arms exhibited greater proliferation reduction than T at this timepoint. Immune expression signatures increased in all arms after one cycle of HER2-targeted therapy, decreasing again by the time of surgery. Our results inform approaches to early assessment of sensitivity to anti-HER2 therapy and shed light on the role of the immune microenvironment in response to HER2-targeted agents. HER2+ breast cancer patients can often develop resistance to trastuzumab and therefore potential combination therapies need to be explored. Here, the authors report the results of a multi-center randomized phase II clinical trial evaluating the pathological and molecular responses associated with trastuzumab and/or lapatinib in combination with chemotherapy in HER2+ breast cancer patients. |
| Databáze: | OpenAIRE |
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