SAN ANTONIO, TX, USA and Neu-Isenburg/Frankfurt, Germany -- December 10, 2014 -- The German Breast Group (GBG) said nab-paclitaxel (ABRAXANE®) demonstrated significant benefit for patients with early high risk breast cancer when compared to conventional solvent-based paclitaxel. The findings are from the GeparSepto clinical trial sponsored by GBG and conducted together with the German AGO-B study group involving over 1200 patients, which is the largest randomized Phase III study ever completed with nab-paclitaxel and the first one completed in high risk early breast cancer. The results were presented by the coordinating investigator Michael Untch, M.D., Berlin in General Session 2 on December 10th, at the 2014 San Antonio Breast Cancer Symposium.
The study found a statistically significant and clinically meaningful 9% absolute improvement from 29% to 38% (p=<0.001) in the pCR (pathological complete response) rate, when neoadjuvant (preoperative) chemotherapy was started with nab-paclitaxel instead of conventional solvent-based paclitaxel followed by epirubicin/cyclophosphamide given all before surgery. Pathological complete response after neoadjuvant treatment for breast cancer is a surrogate marker for long-term efficacy.
"The phase III study provided a head-to-head comparison of weekly nab-paclitaxel with weekly conventional paclitaxel followed by epirubicin/cyclophosphamide in both arms before surgery. Our findings clearly demonstrate nab-paclitaxel is superior to paclitaxel in achieving pCRs in early high risk breast cancer," Prof. Dr. Michael Untch.
"We observed the superior effect of nab-paclitaxel in patients with triple-negative disease (no presence of estrogen, progesterone and HER2 receptor), where the pCR almost doubled with nab-paclitaxel. This is a very important finding, as we know that pCR is most prognostic for outcome in this specific high risk subtype, which comprises about 15% of all breast cancers." highlighted Prof. Dr. Sibylle Loibl, Co-Chair of GBG.
Nab-Paclitaxel encapsulates paclitaxel in near-nano-sized albumin, protein shells. This leverages the natural transport properties of albumin, which allow for higher dose intensity and more drug at the tumor site, compared to solvent based paclitaxel while maintaining tolerability.
The study used a nab-paclitaxel dose of 125mg/m2 for the majority of the patients after an initial higher dose was reduced based on an interim safety analysis. This dose of nab-paclitaxel delivered 56% more chemotherapy to the tumor than conventional paclitaxel. While more patients on nab-paclitaxel discontinued treatment on nab-paclitaxel compared to paclitaxel due to toxicities (17% vs 6%), the vast majority did continue onto the next stage of treatment and surgery. In addition there were fewer incidents of local disease progression (1.7% vs 5%) with nab-paclitaxel compared to solvent-based paclitaxel. Further analysis will be required to determine if toxicities in the nab-paclitaxel arm were reduced with the lower dosing.
"We used the highly effective dual blockade with trastuzumab and pertuzumab simultaneously with the chemotherapy agents for patients in HER2-positive disease, and even in these highly sensitive tumors nab-paclitaxel further improved pCR rates" said Prof. Christian Jackisch from Offenbach, study co-chair of the study.
"This is the first time in 18 years of GBG running neoadjuvant studies in collaboration with AGO-B that pCR rates could be strongly increased by replacing a key component of the standard neoadjuvant chemotherapy instead of just adding additional agents to it. Long-term outcome data have to be awaited to confirm that this short-term benefit to patients is maintained." claimed Prof. Dr. Gunter von Minckwitz, chairman and managing director of GBG and study co-chair of the GeparSepto study.
GBG is a large independent academic network of over 500 study centers in Germany with the world-wide largest experience in conducting neoadjuvant breast cancer trials. Since 1998, with joined forces from AGO-B, over 10.000 patients participated in the neoadjuvant "Gepardo" trial series. GBG has recruited at totality of over 35.000 patients to trials in breast cancer of all indications. Reports on these trials were previously published in the New England Journal of Medicine, The Lancet Oncology, the Journal of Clinical Oncology and the Journal of the National Cancer Institute (for more information go to http://www.