Phase 3 results show significant pathological complete response for nab-paclitaxel in neoadjuvant breast cancer

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, according to data presented at the 2014 San Antonio Breast Cancer Symposium, December 9-13 in San Antonio, Texas.

The findings are from the GeparSepto clinical trial sponsored by GBG and conducted together with the German AGO-B study group involving more than 1,200 patients, which is the largest randomized phase 3 study ever completed with nab-paclitaxel and the first one completed in high-risk early breast cancer.

For the study, patients were randomly assigned into 2 groups of approximately 600 patients each, with palpable tumor size between 5 mm and 150 mm. The median age was about 50 years in both arms, 33% of participants had HER2-positive tumors, and 23% had triple-negative breast cancer.

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The study used a nab-paclitaxel dose of 125 mg/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.

The study found a statistically significant and clinically meaningful 9% absolute improvement from 29% to 38% (P=<.001) in the pCR (pathological complete response) rate when neoadjuvant (preoperative) treatment was started with nab-paclitaxel instead of conventional solvent-based paclitaxel followed by epirubicin/cyclophosphamide given before surgery.

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“Because pCR is a surrogate marker for long-term efficacy, our findings clearly demonstrate nab-paclitaxel is superior to paclitaxel in early high-risk breast cancer based on this early finding,” said coordinating investigator Michael Untch, MD, head of the Breast Cancer Center at HELIOS Klinikum Berlin-Buch in Berlin, Germany.

“Of special importance, we observed that with nab-paclitaxel the pCR almost doubled in patients with triple-negative disease that comprises about 15% of all breast cancers, and can be especially difficult to treat,” Dr Untch said.

“As researchers we want to see longer-term follow-up before recommending that treatments change based on this finding,” he said. “However, nab-paclitaxel is approved in the metastatic breast cancer setting. This means it is available should treating oncologists decide to use it off-label. And although again, we do not recommend that, a formulary manager should be prepared.”

Current guidelines for neoadjuvant breast cancer patients may include 4 cycles of a taxane, according to Dr Untch.

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“Solvent-based taxanes [paclitaxel, docetaxel] cause severe toxicities not only by the active agents itself, but also by the solvents like cremophor,” he said. “Nab-paclitaxel is a solvent-free formulation of paclitaxel encapsulated in albumin. It does not require premedication with corticosteroids or antihistamines to prevent the risk of solvent-mediated hypersensitivity reactions. This new formulation improves the safety profile, allows higher dosing with shorter infusion duration, and produces higher tumor drug concentration.

“Nab-paclitxel has already demonstrated positive response in metastatic breast cancer,” he continued. “A clinical study of nab-paclitxel versus paclitaxel as neoadjuvant treatment not only allowed us to compare competing treatment approaches with a very high-quality homogenous treatment population [precise assessment of response by histological assessment], but also to utilize predictive markers of longer-term results.”

“The phase 3 study provided a head-to-head comparison of weekly nab-paclitaxel with weekly conventional paclitaxel,” said Dr Untch. “Our findings clearly demonstrate nab-paclitaxel is superior to paclitaxel in achieving pCRs in early high-risk breast cancer.”

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. The GBG Research Institute received unrestricted grants and the provision of medication from Celgene and Roche for the conduct of the GeparSepto study. Nab-paclitaxel is approved in the United States and Europe for patients with metastatic breast cancer.