Pilot trial of preoperative (neoadjuvant) letrozole in combination with bevacizumab in postmenopausal women with newly diagnosed estrogen receptor- or progesterone receptor-positive breast cancer.
BACKGROUND
Tumor content or expression of vascular endothelial growth factor (VEGF) is associated with impaired efficacy of antiestrogen adjuvant therapy. We designed a pilot study to assess the feasibility and short-term efficacy of neoadjuvant letrozole and bevacizumab (anti-VEGF) in postmenopausal women with stage II and III estrogen receptor/progesterone receptor-positive breast cancer.


METHODS
Patients were treated with a neoadjuvant regimen of letrozole orally 2.5 mg/day and bevacizumab intravenously 15 mg/kg every 3 weeks for a total of 24 weeks before the surgical treatment of their breast cancer. Patients were followed for toxicity at 3-week intervals, and tumor assessment (a physical examination and ultrasound) was performed at 6-week intervals. Positron emission tomography (PET) scans were performed before therapy and 6 weeks after the initiation of therapy.


RESULTS
Twenty-five evaluable patients were treated. The regimen was well-tolerated, except in 2 patients who were taken off the study for difficulties controlling their hypertension. An objective clinical response occurred in 17 of 25 patients (68%), including 16% complete responses (CRs) and 52% partial responses. The 4 patients with clinical CRs manifested pathologic CRs in their breasts (16%), although 1 patient had residual tumor cells in her axillary nodes. Eight of 25 patients (32%) attained stage 0 or 1 status. The PET scan response at 6 weeks correlated with clinical CRs and breast pathologic CRs at 24 weeks (P < .0036).


CONCLUSIONS
Combination neoadjuvant therapy with letrozole and bevacizumab was well-tolerated and resulted in impressive clinical and pathologic responses. The Translational Breast Cancer Research Consortium has an ongoing randomized phase II trial of this regimen in this patient population.
Forero-Torres
Andres
A
Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294-3300, USA. andres.forero@ccc.uab.edu
Saleh
Mansoor N
MN
Galleshaw
Janice A
JA
Jones
Cheryl F
CF
Shah
Jatin J
JJ
Percent
Ivor J
IJ
Nabell
Lisle M
LM
Carpenter
John T
JT
Falkson
Carla I
CI
Krontiras
Helen
H
Urist
Marshall M
MM
Bland
Kirby I
KI
De Los Santos
Jennifer F
JF
Meredith
Ruby F
RF
Caterinicchia
Valerie
V
Bernreuter
Wanda K
WK
O'Malley
Janis P
JP
Li
Yufeng
Y
LoBuglio
Albert F
AF
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009570:Nitriles; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; D000068258:Bevacizumab; D000077289:Letrozole