Bevacizumab, Everolimus (RAD001), and Lapatinib as Neoadjuvant Chemotherapy Regimes for Primary Breast Cancer
Status:
Completed
Trial end date:
2015-10-01
Target enrollment:
Participant gender:
Summary
Anthracycline-taxane based chemotherapy regimens are recommended mainly by current guidelines
for neoadjuvant application of systemic treatment. The addition of other cytotoxic agents,
e.g. antimetabolites, vincaalkaloids, or platinum salts resulted in marginal increase in
efficacy, but was associated also with an increase in toxicity. Recently, only the addition
of the Her-2 antibody trastuzumab has significantly improved pathologic response rate.
Therefore, two major strategies are followed in current research projects:
- To improve the selection of patients according to their tumors' sensitivity to
chemotherapy.
- To implement small molecules with specific mechanism of action.
Within the GeparQuinto trial, the first strategy is followed by:
- The PREDICT substudy. A gene signature specific for the response to anthracyclines and
taxanes will be prospectively evaluated for its ability to identify patients with chance
higher than 50% for a pCR. The results may leed to a better risk-benefit ratio for the
use of conventional chemotherapy.
- Adapting further chemotherapy to the response of the tumor to the first couple of
chemotherapy cycles. Based on the previous experience made by the GeparTrio study,
patients not responding early have a low chance to respond with a pCR irrespective of
the type of chemotherapy. So, if further chemotherapy is planned, therapy should be
selected according to a favorable toxicity profile.
The second strategy is followed by investigating in three parallel group comparisons the
efficiency of three distinct small molecules which appear to be generally active in breast
cancer:
- Bevacizumab, an inhibitor of the VEGF pathway targeting tumor neo-angiogenesis.
- Lapatinib, an inhibitor of the Her-1 and Her-2 receptor tyrosine kinase.
- RAD001 (Everolimus), an inhibitor of the mTOR molecule, a central controller of tumor
cell growth and angiogenesis and chemosensitizer.
Treatment for patients participating in the GeparQuinto study will be allocated according to
the Her-2 status of the tumor as well as according to the sonographic response after the
first 4 cycles of treatment. Experimental therapy with bevacizumab, lapatinib, and everolimus
(RAD001) will be randomly added in distinct settings.