Abstract P1-15-02: Long term follow-up of the neo-adjuvant pilot trial evaluating activity of letrozole in combination with bevacizumab in post-menopausal women with newly diagnosed estrogen and/or progesterone receptor positive primary breast cancer
Authors: Forero A , DeLos Santos J , Bowen K , Jones C , Varley KE , Nabell L , Carpenter JT , Falkson CI , Krontiras H , Caterinicchia V , O'Malley J , Li Y , LoBuglio AF , Myers R , Saleh MN 
Published: August 2014

Abstract
Introduction: Vascular endothelial growth factor overexpression has been associated with resistance to anti-estrogen therapy (Cancer Res 2008; 68: 6232); our preclinical data showed that anti-VEGF therapy reverse resistance to estrogen therapy. We postulated that anti-VEGF therapy would enhance anti-estrogen therapy and thus designed a pilot study to assess the feasibility and efficacy of neoadjuvant letrozole and bevacizumab in post-menopausal women with stage II/III, ER/PR positive breast cancer.
Patients and Methods: Eligible patients were treated with a neo-adjuvant regimen of letrozole, 2.5 mg/day (PO) and bevacizumab 15 mg/kg every 3 weeks (IV) for a total of 24 weeks prior to surgical treatment of their breast cancer. Patients were followed for toxicity at three week intervals and for tumor assessment at 6 week intervals. Research tumor biopsies were taken before and 6 weeks after initiation of therapy. The primary endpoint was pathological complete remission (pCR). Patients with inflammatory breast cancer were excluded.
Results: Twenty six patients were enrolled and 25 were treated (one patient had a TIA the day before initiation of therapy). The regimen was well tolerated with 2 patients taken off-study due to uncontrolled hypertension. Objective clinical response occurred in 68% of the patients (17/25), 16% with CR and 52% with partial response (PR). Sixteen percent of the patients (4/25) had clinical stable disease (SD) and 2 patients progressed (PD) while on therapy. Three patients had pCR and 1 patient had microscopic residual tumor cells in the LNs but not in the breast (pCR 16%). Thirty two percent of the patients attained stage 0 or 1 status. None of the pCR patients received adjuvant chemotherapy and none have relapsed after a median follow-up of 6.1 years (range, 5.8+ to 7.5+). Eight of the 13 patients with PR did not receive chemotherapy and only one relapsed with a median follow-up of 6.2 years (range, 3.7 to 7.7+). At a median follow-up of 6.4 years, 88% of the patients have not relapsed and 12% relapsed (1 PD [basal-like], 1 PR [Luminal B], 1 SD [HER2] relapsed at 1.7, 4, and 6.8 years respectively). Of the 17 patients with CR and PR, only 1 has relapsed (6%). Next Generation Sequencing Analysis and evaluation of markers of proliferation/apoptosis are underway.
Conclusion: Combination neoadjuvant therapy with letrozole and bevacizumab was well tolerated and resulted in an impressive pCR of 16%. At a median of 6.4 years, the relapse free survival is 88% for all comers and 94% for responding patients (Luminal A and B). Full correlation of clinical and genomic/biomarker analysis will be presented at the time of the meeting. This encouraging data has led The Breast Cancer Translational Research Consortium to complete a randomized phase II trial (TBCRC002) of letrozole ± bevacizumab in this patient population.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-15-02.