In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 527-527
Abstract:
527 Background: A study from UAB Breast SPORE showed that expression of vascular endothelial growth factor (VEGF) in MCF7 breast tumor xenografts imparts tamoxifen resistance, increases tumor growth and metastatic potential. We postulated that anti-VEGF therapy would enhance anti-estrogen therapy. Methods: Randomized 2:1 phase II selection trial of LET (2.5 mg/day) with/without BEV (anti-VEGF monoclonal antibody; 15 mg/kg q3 weeks) for 24 weeks prior to surgery in post-menopausal patients with stage II/III, ER+/HER2- breast cancer. Primary objective was pathologic complete remission (pCR). Secondary objectives included response rates, down-staging, and toxicity. The trial was not powered to compare arms, but sized to estimate pCR rates to a certain precision (SE 〈 5% for combination, SE 〈 2% for single agent). Biopsies of the tumor and circulating tumor cells were collected. Results: 75 patients were randomized; 50 in the combination and 25 in the LET alone arm; 45 and 24 patients underwent surgery, respectively. Median age was 61 and 65 years, respectively. 5 patients in the combination arm had a pCR (11%; CI 1.9-20.1%) (no evidence of invasive cancer) , and 3 a near pCR (7%; 0%-14.5%) (microscopic disease only); thus pCR/near pCR rate 18% (6.8-29.2%). No patient treated with LET alone achieved a pCR/near pCR. The objective response rate was 64.5% in the combination arm and 37.5% in the single agent arm. 45% of the patients in the combination arm attained stage 0/I; 25% in the letrozole alone arm attained stage I, none attained stage 0. Therapy was well tolerated in both arms with no grade 4/5 toxicity. The most common AEs in the letrozole arm were hot flashes, fatigue, arthralgias/stiffness, myalgias, nausea/vomiting, and night sweats; in the combination arm they were hypertension, arthralgias/stiffness, hot flashes, headache, fatigue, proteinuria, dyspnea, rash, and myalgias. Conclusions: Neoadjuvant therapy with LET and BEV was well-tolerated and resulted in increased objective responses and down-staging. “Next-Gen” genomic analysis of the biopsies will allow for a trial with a targeted patient enrolment. Clinical trial information: F061229006.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.527
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
