GeparSixto (GBG 66)

Carboplatin might improve activity of taxanes in triple-negative disease, as these tumors are more sensitive to DNA damaging agents. Carboplatin might also improve activity in HER2-positive patients as in vivo data demonstrated the highest synergy between trastuzumab, taxanes and carboplatin. Two trials were conducted with this 3 drug combination in HER2-positive advanced disease, one with paclitaxel and another with docetaxel. Whereas adding carboplatin to paclitaxel/trastuzumab reached significantly better results, the docetaxel/carboplatin/ trastuzumab combination failed to show superiority against docetaxel/trastuzumab. One explanation might be that the doses of docetaxel had to be reduced when carboplatin was added, whereas full dose of paclitaxel could be given in the other trial. No randomized data are available for the combination of carboplatin/trastuzumab (+lapatinib) to the more active schedule of weekly paclitaxel as well as for the same combination in addition with an anthracycline.

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 to chemotherapy. Recent data from the Neo-Altto and Neosphere trials suggest that a dual blockage of the HER2 receptor with e.g. trastuzumab and lapatinib reach significantly higher pCR rates than trastuzumab alone and should therefore represent the treatment back-bone of new neoadjuvant trials. A preplanned subgroup analysis of the GeparQuinto study demonstrated that in TNBC the addition of bevacizumab resulted in a significant increase of pCR rates (HR 1.4).

Having a better cardiac tolerability profile compared to conventional anthracyclines, the non-pegylated liposomal encapsulated doxorubicin (NPLD) Myocet® might provide the possibility to combine taxane, anthracycline, platinum salt as well with targeted agents as double HER2 blockage or bevacizumab.

Status:

Recruitment for the GeparSixto study is complete.

A big thank you once again for the implementation of the GeparSixto study to all hospitals of the GBG and the AGO-B!

Top recruiters:

• 51 patients of Prof. Schneeweiss and Team in Heidelberg
• 37 patients of Prof. Salat and Team in München
• 31 patients of Dr. Rezai and Team in Düsseldorf
• 31 patients of Dr. Zahm and Team in Gera
• 26 patients of Dr. Klare and Team in Berlin
• 22 patients of Dr. Tesch and Team in Frankfurt