Background: Anthracycline/taxane based combination chemotherapy of at least 18 weeks represents the standard of care in the neoadjuvant setting. In HER2 positive disease trastuzumab is given concurrently to chemotherapy and achieves a pCR rate (no invasive residuals in breast and nodes) of approx. 40% which can be increased by double anti HER2 blockade by approximately 20%. There are no data on the combination of afatinib (BIBW 2992), an irreversible HER family inhibitor with trastuzumab.

Methods: This is a multi-centre, prospective, open-label phase II study evaluating the efficacy and safety of afatinib in combination with weekly paclitaxel + trastuzumab followed by epirubicin/cyclophosphamide/trastuzumab as neoadjuvant therapy in patients with untreated HER2-positive early breast cancer. Pts with histologically confirmed, centrally reviewed HER2 positive, unilateral, primary operable or locally advanced breast cancer can be included. Tumor size has to be at least 2cm by sonography.

All patients will be treated for a total duration of 30 weeks (6 weeks with afatinib (20mg) and trastuzumab (8/6mg/kg) alone, 12 weeks with weekly paclitaxel (80mg/m2), afatinib and trastuzumab and 12 weeks with epirubicin/cyclophosphamide/trastuzumab according to standard). During the first 2 weeks afatinib 20 mg will be given only every other day to reduce the risk of diarrhea and skin toxicities. Primary prophylaxis with loperamide 2×2 mg daily is obligatory during the first 4 weeks of afatinib/trastuzumab and the first 2 weeks of afatinib/trastuzumab/paclitaxel. Thereafter prophylaxis with loperamide can be stopped if no diarrhea grade > 1 occurred.

Primary objective is pathological complete response (pCR = ypT0/is ypN0). Secondary objectives are pCR by other definitions, clinical response rates, rate and type of surgery, toxicity and compliance, pCR related to skin toxicity and diarrhoea and pre-specified molecular markers. An extensive biomaterial collection is integreated, including obligatory biomaterial (e.g. skin biopsies) collection at baseline, prior to start of paclitaxel at the end of paclitaxel and prior to surgery.

Neoadjuvant anthracycline-taxane-based chemotherapy given simultaneously with trastuzumab after central HER 2-testing results in a pCR rate of approx. 50%. The addition of a dual anti HER2 blockade to chemotherapy increased the pCR by absolute 20%. A pCR rate of 70% is expectedand and a pCR rate of 55% or lower excluded; with α=0.1 and 1-ß=80%, this requires 65 evaluable patients for two-sided one group χ2-test. An integrated safety phase is planned for the first 15 patients entering the study.

The trial is registered under NCT015591477. It is financially supported by Boehringer Ingelheim.

Results: Centres have been initiated after approval by ethics committee and authorities. Three patients have been recruited. It is planned to recruit 12 months in 15 sites in Germany.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT1-1-13.

This abstract was not presented at the conference.