A study of pre-operative (neoadjuvant) letrozole in combination with bevacizumab in post-menopausal women with newly diagnosed operable breast cancer: A preliminary safety report

Document Type

Article

Department

Haematology and Oncology, East Africa

Abstract

Background: Our 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 hormonal therapy would be more effective than hormonal therapy alone for breast cancer.

Methods: Post-menopausal patients with ER and/or PR positive and Her-2-neu negative operable (T2–4a-c/N 0–2/M0) breast cancer were enrolled. Patients received letrozole (2.5 mg po daily) and Bevacizumab (15 mg/kg IV q 3 wks). Patients were reevaluated every 6 wks for a total of 24 wks; patients with CR/PR/SD in the first evaluation continued in the trial; after an additional 6 weeks of therapy patients with PD or SD were taken off-study and only patients with PR/CR completed 24 weeks of therapy. Definitive surgery was performed at the discretion of the surgeon no sooner than 4 wks after the last dose of bevacizumab. Patients continued letrozole while waiting for surgery. Up to December 2006, 27 patients have been enrolled with 13 patients too early to evaluate.

Results: The 14 patients off-study had a median age of 63 years (range; 56 to 79) and an ECOG score of 0 for all patients. None of the patients received therapy for breast cancer before enrollment in the trial. 11 patients were stage II and 3 patients stage III. No treatment-related severe adverse events were seen. Treatment related toxicities were: grade 3 hypertension (n=1), grade 2 hypertension (n=7), grade 2 fatigue (n=2), grade 2 joint pain (n=3), grade 2 hot flashes (n=2), grade 1 proteinuria (n=1); 2 patients were taken off-study because of uncontrolled hypertension occurring on initial infusion of bevacizumab (not evaluable for efficacy). Of the 12 patients evaluable for response, 2 patients had pCR, 8 PR and 2 PD (at 9 weeks and 16 weeks). There have been no problems with wound healing or bleeding related to surgery or progressive disease while awaiting surgery.

Conclusions: Combination 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.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Journal of Clinical Oncology

DOI

https://doi.org/10.1200/jco.2007.25.18_suppl.11020

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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