TBCRC 002: a phase II, randomized, open-label trial of preoperative letrozole with or without bevacizumab in postmenopausal women with newly diagnosed stage 2/3 hormone receptor-positive and HER2-negative breast cancer
Autor: | Brian S. Roberts, Andres Forero-Torres, Lisa A. Carey, Anna Maria Storniolo, Richard M. Myers, Nan Lin, Rita Nanda, Minetta C. Liu, Katherine E. Varley, Yufeng Li, Albert F. LoBuglio, Hope S. Rugo, Christos Vaklavas, Mansoor N. Saleh, William E. Grizzle, Jennifer F. Delossantos, Shannon Puhalla |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Receptor
ErbB-2 Preoperative therapy Gastroenterology chemistry.chemical_compound 0302 clinical medicine Breast cancer Luminal breast cancer Antineoplastic Combined Chemotherapy Protocols Aged 80 and over 0303 health sciences Proteinuria medicine.diagnostic_test Hormone receptor-positive breast cancer Letrozole Middle Aged lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 3. Good health Postmenopause Vascular endothelial growth factor Bevacizumab Receptors Estrogen 030220 oncology & carcinogenesis Postmenopausal Female medicine.symptom Receptors Progesterone Research Article medicine.drug medicine.medical_specialty Neoplasms Hormone-Dependent Breast Neoplasms lcsh:RC254-282 03 medical and health sciences Internal medicine Biopsy Biomarkers Tumor medicine Humans Adverse effect Aged Neoplasm Staging 030304 developmental biology business.industry medicine.disease Discontinuation chemistry Transcriptome business |
Zdroj: | Breast Cancer Research, Vol 22, Iss 1, Pp 1-15 (2020) Breast Cancer Research : BCR |
Popis: | Background In preclinical studies, the expression of vascular endothelial growth factor (VEGF) in hormone receptor-positive breast cancer is associated with estrogen-independent tumor growth and resistance to endocrine therapies. This study investigated whether the addition of bevacizumab, a monoclonal antibody against VEGF, to letrozole enhanced the antitumor activity of the letrozole in the preoperative setting. Methods Postmenopausal women with newly diagnosed stage 2 or 3 estrogen and/or progesterone receptor-positive, HER2-negative breast cancer were randomly assigned (2:1) between letrozole 2.5 mg PO daily plus bevacizumab 15 mg/kg IV every 3 weeks (Let/Bev) and letrozole 2.5 mg PO daily (Let) for 24 weeks prior to definitive surgery. Primary objective was within-arm pathologic complete remission (pCR) rate. Secondary objectives were safety, objective response, and downstaging rate. Results Seventy-five patients were randomized (Let/Bev n = 50, Let n = 25). Of the 45 patients evaluable for pathological response in the Let/Bev arm, 5 (11%; 95% CI, 3.7–24.1%) achieved pCR and 4 (9%; 95% CI, 2.5–21.2%) had microscopic residual disease; no pCRs or microscopic residual disease was seen in the Let arm (0%; 95% CI, 0–14.2%). The rates of downstaging were 44.4% (95% CI, 29.6–60.0%) and 37.5% (95% CI, 18.8–59.4%) in the Let/Bev and Let arms, respectively. Adverse events typically associated with letrozole (hot flashes, arthralgias, fatigue, myalgias) occurred in similar frequencies in the two arms. Hypertension, headache, and proteinuria were seen exclusively in the Let/Bev arm. The rates of grade 3 and 4 adverse events and discontinuation due to adverse events were 18% vs 8% and 16% vs none in the Let/Bev and Let arms, respectively. A small RNA-based classifier predictive of response to preoperative Let/Bev was developed and confirmed on an independent cohort. Conclusion In the preoperative setting, the addition of bevacizumab to letrozole was associated with a pCR rate of 11%; no pCR was seen with letrozole alone. There was additive toxicity with the incorporation of bevacizumab. Responses to Let/Bev can be predicted from the levels of 5 small RNAs in a pretreatment biopsy. Trial registration This trial is registered with ClinicalTrials.gov (Identifier: NCT00161291), first posted on September 12, 2005, and is completed. |
Databáze: | OpenAIRE |
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