Primary efficacy analysis of a phase II study of neoadjuvant bevacizumab (BEV), chemotherapy (CT), and trastuzumab (H) in HER2-positive inflammatory breast cancer (IBC): BEVERLY2 study.

Abstract

531 Background: In HER2-negative metastatic breast cancer, BEV significantly improves the efficacy of first-line CT, as shown in three phase III trials. The role of H in HER2-positive breast cancer is established but there is less information on BEV in this setting. Methods: The primary objective of this single-arm, open-label, phase II study is to determine the rate of pathologic complete response (pCR; Sataloff classification) by central review in patients (pts) receiving neoadjuvant CT, BEV, and H for IBC. Secondary endpoints include pCR rate by investigator assessment, disease-free survival, overall survival, safety (CTCAE v3), and potential predictive markers. Pts with HER2-positive IBC (IHC 3+ or FISH/CISH+, T4d, any N) received 4 cycles of FEC100+ BEV 15 mg/kg, d1 q21d, followed by 4 cycles of docetaxel 100 mg/m2 + BEV 15 mg/kg + H 8→6 mg/kg q21d. Pts underwent surgery 4–6 weeks after the last dose, followed by radiotherapy. H was continued during surgery and radiotherapy and as adjuvant therapy. BEV was re-introduced as adjuvant therapy for 10 cycles, giving a total of 18 cycles each of BEV and H. Results: Between Oct 2008 and Oct 2009, 52 pts were included (median age 52 years; Scarff-Bloom–Richardson grade 2 in 40% of pts and 3 in 50%). All 8 cycles of neoadjuvant therapy were completed as planned by 42 pts (81%); 45 (87%) received 8 cycles of BEV and 50 (96%) received ≥4 preoperative cycles of H. The pCR rate was 63.5% by central review (95% CI 49.4–77.5%). Investigator-assessed pCR rate was 67.3% (95% CI 53.6–81.0%). The clinical response rate was 98% in 45 pts with data available. Grade ≥3 adverse events (AEs) in >5% of pts were: neutropenia (48% of pts); febrile neutropenia (17%); alopecia (10%); hand-foot syndrome, leukopenia, febrile bone marrow aplasia, increased 𝛄-glutamyltransferase (each 8%); anemia and mucositis (each 6%). There was only 1 grade ≥3 AE of special interest for BEV (hypertension in 1 pt). Three pts (6%) experienced cardiac failure (all grade 2, resolved). There were no treatment-related deaths. Conclusions: Neoadjuvant BEV, H, and CT is highly active in IBC (pCR rate 63.5%) with an acceptable safety profile.