A phase II study investigating dual HER2 blockade with afatinib and trastuzumab in combination with neoadjuvant chemotherapy in patients with HER2-positive primary breast cancer.
Introduction
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 simultaneously. Neoadjuvant anthracycline-taxane-based chemotherapy given simul-taneously with trastuzumab achieves a pCR rate of approx. 40%.
Recent data showed that a double blockade of the HER2 receptor (e.g. trastuzumab + lapatinib; trastuzumab + pertuzumab) given together with a few cycles of chemotherapy can increase the pCR rate by approximately 20%.
So far, there is uncertainty, if afatinib (BIBW 2992), an irreversible HER family blocker can lead to an even more complete blockade of the HER2 pathway when given in combination with trastuzumab.
The neoadjuvant setting provides the unique opportunity to assess precisely and at short term the effect of systemic treatment by assessing the pCR at surgery. It also allows treating patients with HER2 positive breast cancer before surgery without standard trastuzumab treatment, as, according to current guideline, trastuzumab can also be given sequentially after surgery.
The aim of the study is to show that chemotherapy + trastuzumab + afatinib can achieve significant pCR rates.
A 6 weeks window of afatinib + trastuzumab before start of chemotherapy will allow to examine early biomarker changes and clinical response to the chemotherapy free double blockade of HER2 which can be indirectly compared with results from the pre-chemotherapy part of NeoALTTO.
News
The study is completed.
Design
The DAFNE study is a multicenter, prospective, open-label phase II study evaluating the efficacy and safety of afatinib and trastuzumab in combination, followed by afatinib and trastuzumab with weekly paclitaxel and epirubicin, cyclophosphamide and trastuzumab as neoadjuvant therapy in patients with untreated, primary HER2-positive breast cancer.
All patients will be treated as follows for a total duration of 30 weeks:
- 6 weeks Afatinib and Trastuzumab,
- 12 weeks Afatinib (-1 week), Paclitaxel weekly and Trastuzumab,
- 12 weeks Epirubicin, Cyclophosphamid and Trastuzumab.
