A pilot open-label trial of preoperative (neoadjuvant) letrozole in combination with bevacizumab in postmenopausal women with newly diagnosed operable breast cancer
Document Type
Article
Department
Haematology and Oncology, East Africa
Abstract
Background: Preclinical studies suggest that up-regulation of tumor cell VEGF is a mechanism to subvert estrogen dependence in hormone responsive breast cancer resulting in reduced efficacy or acquired resistance; we hypothesized that the combination of bevacizumab (an anti-VEGF MoAb) and hormone therapy would be more effective than hormone therapy alone for the treatment of breast cancer.
Methods: Postmenopausal, ER and/or PR positive and Her-2-neu negative, operable (T2–4a-c/N 0–2/M0) breast cancer patients were enrolled. Patients received letrozole (2.5 mg po daily) and bevacizumab (15 mg/kg IV q 3 wks). Patients were evaluated every 6 wks; patients with CR/PR/SD in the first evaluation continued; after an additional 6 weeks of therapy patients with PD or SD were taken off-study and those patients with PR/CR completed 24 weeks of therapy. Definitive surgery was performed no sooner than 4 wks after the last dose of bevacizumab. Patients continued letrozole while waiting for surgery. 26 patients were enrolled with 1 patient too early to evaluate (Dec 2007).
Results: The 25 patients that completed the study had a median age of 63 years (range; 54 to 79) and an ECOG score of 0 for all patients. 20 patients were stage II and 6 patients stage III. No treatment-related severe adverse events were seen. Treatment-related toxicities were as follows: 2 patients were taken off-study because of uncontrolled hypertension occurring on initial infusion of bevacizumab, grade 3 hypertension (n=5), grade 2 hypertension (n=7), grade 2 fatigue (n=4), grade 2 joint pain (n=3), grade 2 hot flashes (n=2), grade 1 proteinuria (n=1). Of the 22 patients evaluable for response, 4 patients had pCR in the breast (18%) and 3 of them had negative lymph nodes, 6 patients had a PR greater than 80% (28%), 6 patients had a PR between 20–80% (28%) and 2 patients had PD (at 9 weeks and 16 weeks). Overall response (CRs and PRs) 74%. There have been no problems with wound healing or bleeding related to surgery or progressive disease while awaiting surgery.
Conclusions: Combination of letrozole and bevacizumab has substantial clinical efficacy and is well tolerated. The combination therapy will be evaluated in a randomized Breast Cancer Research Consortium Trial.
Publication (Name of Journal)
Journal of Clinical Oncology
DOI
https://doi.org/10.1200/jco.2008.26.15_suppl.625
Recommended Citation
Forero-Torres, A.,
Galleshaw, J.,
Jones, C.,
Percent, I.,
Nabell, L.,
Carpenter, J.,
Falkson, C.,
Krontiras, H.,
Bland, K.,
Saleh, M.
(2008). A pilot open-label trial of preoperative (neoadjuvant) letrozole in combination with bevacizumab in postmenopausal women with newly diagnosed operable breast cancer. Journal of Clinical Oncology, 26(15).
Available at:
https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/35
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Comments
This work was published before the author joined Aga Khan University.