Feasibility trial of letrozole in combination with bevacizumab in patients with metastatic breast cancer Journal Article


Authors: Traina, T. A.; Rugo, H. S.; Caravelli, J. F.; Patil, S.; Yeh, B.; Melisko, M. E.; Park, J. W.; Geneus, S.; Paulson, M.; Grothusen, J.; Seidman, A. D.; Fornier, M.; Lake, D.; Dang, C.; Robson, M.; Theodoulou, M.; Flombaum, C. D.; Norton, L.; Hudis, C. A.; Dickler, M. N.
Article Title: Feasibility trial of letrozole in combination with bevacizumab in patients with metastatic breast cancer
Abstract: Purpose Preclinical models suggest that the use of anti-vascular endothelial growth factor (anti-VEGF) therapy with antiestrogens may prevent or delay the development of endocrine therapy resistance. We therefore performed a feasibility study to evaluate the safety of letrozole plus bevacizumab in patients with hormone receptor-positive metastatic breast cancer (MBC). Methods Patients with locally advanced breast cancer or MBC were treated with the aromatase inhibitor (AI) letrozole (2.5 mg orally daily) and the anti-VEGF antibody bevacizumab (15 mg/kg intravenously every 3 weeks). The primary end point was safety, defined by grade 4 toxicity using the National Cancer Institute Common Toxicity Criteria, version 3.0. Secondary end points included response rate, clinical benefit rate, and progression-free survival (PFS). Prior nonsteroidal AIs (NSAIs) were permitted in the absence of progressive disease. Results Forty-three patients were treated. After a median of 13 cycles (range, 1 to 71 cycles), select treatment-related toxicities included hypertension (58%; grades 2 and 3 in 19% and 26%), proteinuria (67%; grades 2 and 3 in 14% and 19%), headache (51%; grades 2 and 3 in 16% and 7%), fatigue (74%; grades 2 and 3 in 19% and 2%), and joint pain (63%; grades 2 and 3 in 19% and 0%). Eighty-four percent of patients had at least stable disease on an NSAI, confounding efficacy results. Partial responses were seen in 9% of patients and stable disease >= 24 weeks was noted in 67%. Median PFS was 17.1 months. Conclusion Combination letrozole and bevacizumab was feasible with expected bevacizumab-related events of hypertension, headache, and proteinuria. Phase III proof-of-efficacy trials of endocrine therapy plus bevacizumab are in progress (Cancer and Leukemia Group B 40503).
Keywords: survival; treatment; endocrine therapy; phase-iii; women; estrogen-receptor; endothelial growth-factor; randomized-trial; postmenopausal; adjuvant; paclitaxel plus bevacizumab; tamoxifen therapy
Journal Title: Journal of Clinical Oncology
Volume: 28
Issue: 4
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2010-02-01
Start Page: 628
End Page: 633
Language: English
ACCESSION: ISI:000274138800018
DOI: 10.1200/jco.2009.21.8784
PROVIDER: wos
PUBMED: 19841327
PMCID: PMC3940895
Notes: --- - Article - "Source: Wos"
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MSK Authors
  1. Sujata Patil
    383 Patil
  2. Andrew D Seidman
    244 Seidman
  3. Clifford Hudis
    840 Hudis
  4. Larry Norton
    562 Norton
  5. Mark E Robson
    365 Robson
  6. Chau Dang
    156 Dang
  7. Diana E Lake
    70 Lake
  8. Maura N Dickler
    237 Dickler
  9. Monica Nancy Fornier
    136 Fornier
  10. Tiffany A Traina
    153 Traina
  11. Stephanie Geneus
    6 Geneus