Abstract P6-12-06: Three-year follow up results of a phase II study of neoadjuvant bevacizumab, chemotherapy, and trastuzumab in HER2-positive inflammatory breast cancer: BEVERLY2 study

Abstract

Abstract Background: Bevacizumab (Bev) and trastuzumab (H) are proven treatments of advanced or HER2-positive metastatic breast cancer; however, few data exist for these drugs in inflammatory breast cancer (IBC). The aim of our study was to assess efficacy and safety of neoadjuvant Bev combined with H and chemotherapy (CT) in patients (pts) with primary HER2 positive IBC. The primary endpoint of the study, pathological complete response (pCR) rate by central review according to Sataloff classification, has been previously reported (pCR = 63.5%) together with circulating tumor cells (CTC) and circulating endothelial cells (CEC) detection rates and changes during treatment (Pierga et al, Lancet Oncol 2012). In the present abstract we are reporting the 3 year follow up analysis results. Methods: In this phase 2, multicentre, open-label, single-arm, non-comparative trial, we enrolled women with histologically confirmed HER2-positive non-metastatic IBC. The primary endpoint was to determine the rate of pCR; secondary endpoints included disease-free survival (DFS), overall survival (OS), safety (CTCAE v3) and potential predictive markers. Pts 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 (RT). H was continued during surgery and RT 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. CTC and CEC were detected by the CellSearch system. Results: We enrolled 52 pts in 21 centers; 42 (81%) of 52 pts received all eight cycles of neoadjuvant therapy, 49 pts (94%) underwent surgery; 48 pts (92%) received adjuvant treatment and 44 pts (85%) were followed during 3 years (there were 8 withdrawals from study treatment period). Grade ≥3 adverse events (AEs) in >5% of pts were: neutropenia (44% of pts); febrile neutropenia (29%); alopecia and leukopenia (10%), hand-foot syndrome and febrile bone marrow aplasia (8%), increased γ-glutamyltransferase (8%), anemia, hypertension and mucositis (each 6%). There were 9 pts with grade ≥3 AE of special interest for BEV: hypertension in 3 pt; proteinuria in 2 pts; postoperative wound complication, infected lymphocele, incision site abscess and impaired healing in 1 pt each and cardiac failure in 1 pt. Ten pts developed a cardiac failure (Grade ≥1), which was mostly Grade 2 and resolved in all cases. There was no treatment-related death. Median follow-up was 36 months. 3-year DFS rate was 67.8% [52.8- 79.0] and OS rate was 89.8% [77.2- 95.6]. pCR was significantly associated with DFS: 3 year DFS rate was 78% [95% CI:58- 89] in pts with pCR vs 53% [95% CI:29- 72] in pts without pCR (p = 0.0445). CTC positivity (≥1CTC/7.5ml) at baseline (35% of pts) was also strongly associated with lower DFS rate (3 year DFS: 43% [95% IC: 20- 64] vs 81% [95% IC: 62- 91], p<0.01). Conclusion: Neoadjuvant BEV, H, and CT is highly active in IBC (3-y DFS 67.8%) with an acceptable safety profile. CTC positivity (≥1CTC/7.5ml) at baseline and pCR at the end of neoadjuvant treatment are two prognostic factors for DFS in non-metastatic IBC. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-12-06.