[4107] Preliminary safety results: addition of bevacizumab to 3 docetaxel regimens as adjuvant therapy for early stage breast cancer.

Yardley DA, Hart L, Waterhouse DM, Badarinath S, Daniel B, Cook D, Thompson J, Childs BH, Burris HA Tennessee Oncology, Nashville; Florida Cancer Specialists, Fort Myers; Oncology Hematology Care, Cincinnati; Integrated Community Oncology Network, Jacksonville; Chattanooga Oncology and Hematology Associates, Chattanooga; Sanofi-aventis, Bridgewater

Background: Docetaxel-containing chemotherapy regimens improve disease-free survival (DFS) and overall survival in early stage breast cancer (BC) patients (pts). Bevacizumab (Bev) improves response rate and DFS in metastatic BC. This trial evaluates the feasibility of adding Bev to 3 adjuvant docetaxel BC regimens. Primary endpoint is cardiac safety (G3/4 congestive heart failure [CHF]).
Materials and Methods: Phase IIb, randomized, non-comparative study. Planned accrual: 225 pts (75/arm) with previously-untreated node-positive or high-risk node-negative BC. Eligibility: operable invasive adenocarcinoma 4 wks from surgery, normal cardiac function, known HER2 status. Pts with cardiac disease/risk of cardiac disease were not eligible. HER2 normal pts were randomized to (mg/m² unless stated otherwise) Arm A (ACT): doxorubicin (A) 60 + cyclophosphamide (C) 600 q3w x 4 followed by docetaxel (T) 100 x 4 or Arm B (TAC): T 75 + A 50 + C 500 q3w x 6. FISH HER2+ pts received Arm C (TCH): T 75 + carboplatin AUC 6 q3w x 6 + trastuzumab (H) 6 mg/kg q3w x 52 wks. Bev 15 mg/kg q3w beginning Day 1 x 52 wks was administered in all arms. Granulocyte growth factor prophylaxis was mandated in all arms.
Results: Safety data are available for the first 138 pts (Arm A=53, Arm B=52, Arm C=33) receiving 4 cycles of treatment. Grade 3/4 toxicities (Arms A, B, C) included: neutropenia (n = 24, 22, 2), febrile neutropenia (5, 9, 0), leukopenia (10, 14, 1), thrombocytopenia (3, 7, 0) and fatigue (11, 3, 0). One on-study death occurred in Arm B from neutropenic enterocolitis. Documented CHF was reported in 3 pts (A=1, B=2), 2 occurring at the start of maintenance therapy. No cardiac events have been noted with Bev and H in Arm C. A total of 29 (21%) pts prematurely discontinued study treatment. Radiation therapy prior to study entry was administered in 4 pts (1, 1, 2). Concurrent Bev and adjuvant breast irradiation was administered in: Arm A=7 (13.2%), Arm B=15 (28.8%), Arm C=5 (15.2%). Most common AEs (Arms A, B, C) in these pts were: radiation skin injury (2, 2, 2), arthralgia (6, 4, 1), myalgia (4, 4, 1), bone pain (0, 4, 2), extremity pain (2, 1, 2), and rash (3, 3, 0).
Discussion: Preliminary data show an acceptable early safety profile, with no unexpected toxicity, when Bev was added to docetaxel adjuvant BC regimens. The addition of Bev did not result in increased risk of toxicity from standard radiotherapy administered either prior to or while on-study. Three early CHF events were observed; all occurred in pts receiving anthracyclines. No cardiac events have been identified with the Bev/trastuzumab combination. Accrual to the trial is ongoing. Updated results will be presented.
Support: sanofi-aventis,US.

Saturday, December 13, 2008 7:00 AM

Poster Session IV: Treatment: Adjuvant Chemotherapy (7:00 AM-9:00 AM)