AVATAXHER: An open-label, randomized, multicenter study investigating the addition of bevacizumab (B) to neoadjuvant trastuzumab (T) plus docetaxel (D) in patients with early stage HER2-positive breast cancer (HER2+ BC) stratified according to PET change after one therapy cycle.

Breast Cancer - HER2/ER
Session Type and Session Title: 
Oral Abstract Session, Breast Cancer - HER2/ER
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 507)
Bruno P. Coudert, Jean-Yves Pierga, Marie-Ange Mouret-Reynier, Khaldoun Kerrou, Jean-Marc Ferrero, Thierry Petit, Pierre Kerbrat, Pierre-Francois Dupre, Thomas Denis Bachelot, Philippe Gabelle, Sylvia Giard, David Coeffic, Philippe Bougnoux, Jean Briac Prevost, Gilles Paintaud, Gilles Thibault, Juana Hernandez, Mathieu Coudert, Laurent Arnould, Alina Berriolo-Riedinger; Department of Medical Oncology, Centre Georges-Francois Leclerc, Dijon, France; Department of Medical Oncology, Institut Curie, Paris, France; Department of Medical Oncology, Centre Jean Perrin, Clermont-Ferrand, France; Department of Nuclear Medicine, Hopital Tenon, Paris, France; Centre Antoine Lacassagne, Department d'Oncologie Medicale, Nice, France; Department of Medical Oncology, Centre Paul Strauss, Strasbourg, France; Centre Eugène Marquis, Rennes, France; Service de Gynécologie, Hôpital Cavale Blanche, Brest, France; Département d'Oncologie Médicale, Centre Léon Berard, Lyon, France; Department of Surgery, Institut Daniel Hollard, Grenoble, France; Department of Surgery, Centre Oscar Lambret, Lille, France; Department of Medical Oncology, Clinique Hartmann, Neuilly sur Seine, France; Department of Medical Oncology, CHU Bretonneau, Tours, France; Department of Medical Oncology, Centre Pierre Curie, Beuvry, France; Pharmacology Department, CHU Bretonneau, Tours, France; Immunology Department, CHU Bretonneau, Tours, France; Roche SAS, Boulogne-Billancourt, France; Experis IT, Nanterre, France; Department of Pathology, Centre Georges-Francois Leclerc, Dijon, France; Department of Nuclear Medicine, Centre Georges-Francois Leclerc, Dijon, France

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Abstract Disclosures


Background: T-based neoadjuvant chemotherapy achieves pCR rates of ~50% in HER2+ BC, enabling frequent conservative surgery. Pre-clinical and clinical data support the synergistic combination of B and T. The ph II AVATAXHER trial (EUDRACT 2009-013410-26) investigated whether adding B to neoadjuvant T+D improved pCR rates in tumors with a low likelihood of attaining pCR (predicted based on relative change in FDG tumoral uptake [ΔSUV] after one cycle of T+D). Methods: Patients were ≥18 yrs old with stage T2/3, N0/1 HER2+ BC. Patients received two 3-weekly cycles of T (8 mg/kg, then 6 mg/kg) and D (100 mg/m2). Those with ≥70% ΔSUV in PET values between cycle 1 and 2 received four more cycles of T+D, one cycle of T, then surgery (standard arm). Those with <70% ΔSUV were randomized 2:1 to four cycles of T+D+B (15 mg/kg; arm a) or T+D (arm b), then one T cycle and surgery. The primary endpoint was pCR rate at surgery. The positive (PPV) and negative predictive value (NPV) of ΔSUV on pCR rate and safety were also investigated. Results: 152 patients were recruited at 26 sites (10 were withdrawn pretreatment; ITT=142). 37/69 (53.6%) patients in the standard arm achieved pCR, 21/48 (43.8%) in arm a and 6/25 (24.0%) in arm b. pCR rates in patients with hormone receptor –ve/+ve disease were: 69.0%/42.5% (standard arm), 57.9%/34.5% (arm a), and 40.0%/13.3% (arm b). Surgery (133 pts) was conservative in 84.8% of patients with surgery in the standard arm, 67.4% in arm a, and 62.5% in arm b. In patients without B, ΔSUV after one cycle predicted pCR with a PPV of 52.9% and a NPV of 75%. Toxicity was mild and included asthenia, myalgia, and increased lacrimation (all pts had ≥1 AE). Grade 3/4 AEs (in 31% of pts) included neutropenia (8.6% pts), febrile neutropenia (3.6%), myalgia (3.6%), asthenia (2.9%), and nail toxicity (2.9%). Conclusions: Adding B to neoadjuvant T+D, in tumors with a low likelihood of pCR predicted by PET ΔSUV, increased the pCR rate from 24.0% to 42.5%. PET ΔSUV, by selecting low responding HER2+ tumors, may be a useful tool for optimizing neoadjuvant therapy for HER2+ BC. Clinical trial information: 2009-013410-26.