S5-6: Neoadjuvant Pertuzumab and Trastuzumab Concurrent or Sequential with an Anthracycline-Containing or Concurrent with an Anthracycline-Free Standard Regimen: A Randomized Phase II Study (TRYPHAENA).

Abstract Background: Pertuzumab (P) is a fully humanized investigational monoclonal antibody that binds to human epidermal growth factor receptor 2 (HER2), preventing homo- and heterodimerization of HER2 and other HER family members and inducing antibody-dependent cell-mediated cytotoxicity. The NeoSphere study demonstrated significantly increased antitumor activity in the neoadjuvant setting for the combination of P and trastuzumab (H) plus docetaxel (T) compared with HT alone (Gianni et al. SABCS 2010), consistent with the hypothesis of complementary mechanisms of action of P and H. No increase in cardiac risk was observed with the addition of P to H and HT regimens. Anthracyclines have an important role in the treatment of breast cancer and may be especially efficacious in HER2−positive disease. In the TRYPHAENA study, P and H are being administered either sequentially or concurrently with an anthracycline-containing or concurrently with an anthracycline-free standard regimen in order to establish the tolerability profile of these regimens for testing in the adjuvant setting. Methods: Patients with centrally confirmed stage II or III (including locally advanced and inflammatory disease) HER2−positive breast cancer (defined as centrally confirmed HER2 IHC 3+ or FISH/CISH+) were randomized to receive: Study medication: P 840 mg loading dose and 420 mg maintenance; H 8 mg/kg loading dose and 6 mg/kg maintenance; T was given at 75 mg/m2 with dose escalation to 100 mg/m2 if the starting dose was well tolerated (no dose escalation in Arm C); FEC (5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 600 mg/m2) and carboplatin AUC 6. All treatments were given intravenously q3w. The study is ongoing. All patients will receive H for 1 year. The primary endpoint is assessment of the safety and tolerability of neoadjuvant treatment. During neoadjuvant treatment, left ventricular ejection fraction is assessed at Cycles 2, 4, and 6 by echocardiogram or multiple-gated acquisition. Safety data are supervised by a data and safety monitoring board. The key secondary endpoint is the rate of pathological complete response (pCR) defined as absence of invasive disease in the breast at surgery. Tissue specimens at baseline and post-surgery were required for all patients. This study is registered at ClinicalTrials.gov: NCT00976989. Results: 225 patients have been recruited. No arm has required modification due to safety concerns or to excessive incidence of disease progression. Analysis of the study results is anticipated in Q3 2011. Safety/tolerability and efficacy (pCR) data will be presented. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S5-6.