Abraxane Wins Neoadjuvant Taxane Battle in Breast Cancer Trial

Abraxane (nab-paclitaxel) proved markedly more effective than conventional paclitaxel as part of a neoadjuvant regimen for patients with high-risk, early breast cancer, according to results presented at the 2014 San Antonio Breast Cancer Symposium.

The GeparSepto study found that 38 percent of patients who received Abraxane during the randomized phase 3 trial achieved a pathologic complete response (pCR), compared with 29 percent of participants who were given conventional paclitaxel, according to results announced by the German Breast Group (GBG). The 9 percent absolute improvement is statistically significant and clinically meaningful, the group said.

The results are particularly noteworthy because pCR rates were “strongly increased by replacing a key component of the standard neoadjuvant chemotherapy instead of just adding additional agents to it,” Gunter von Minckwitz, chairman and managing director of GBG, said in a statement.

Von Minckwitz, who also served as co-chair of the GeparSepto trial, said it was the first time that substituting a single agent in a drug regimen had made such an impact in 18 years of collaboration on neoadjuvant breast cancer studies involving the GBG and the German Gynecological Oncology Working Group-Breast (AGO-B).

He noted that “long-term outcome data have to be awaited to confirm that this short-term benefit to patients is maintained.”

Other GBG researchers also were enthusiastic about the impact of Abraxane as part of the neoadjuvant repertoire.

The phase 3 study provided a head-to-head comparison of weekly Abraxane 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,” coordinating investigator Michael Untch, of Helios Klinikum Berlin-Buch, who presented the study results at the symposium Wednesday, said in the GBG statement.

Differences in the Two Drugs

Abraxane is an albumin-encapsulated nanoparticle formulation of the taxane paclitaxel that delivers “higher dosing with shorter infusion duration and produces higher tumor drug concentration” to the tumor site than conventional paclitaxel, the GBG investigators said in the clinical trial protocol.

Moreover, Abraxane is solvent-free, resulting in an improved safety profile compared with the solvent-based paclitaxel and eliminating the need for premedication to prevent hypersensitivity reactions, the researchers noted.

Abraxane is approved by the Food and Drug Administration (FDA) for the treatment of patients with metastatic breast cancer whose disease has progressed after combination chemotherapy or who have relapsed within 6 months of adjuvant chemotherapy.

Head-to-Head Comparison

The GeparSepto trial tested Abraxane in the neoadjuvant setting, where conventional paclitaxel has been incorporated into standard chemotherapy regimens.

The study recruited more than 1,200 patients with untreated cancer and no clinically relevant cardiovascular or other comorbidities. The median age was about 50 years in both arms, 33 percent of participants had HER2-positive tumors, and 23 percent had triple-negative breast cancer.

The participants were randomized 1:1 to receive either Abraxane or paclitaxel followed by epirubicin plus cyclophosphamide. Patients with HER2-positive disease also received targeted therapies Herceptin (trastuzumab) and Perjeta (pertuzumab).

Investigators said they started the trial with a higher dosage of Abraxane (150 mg/m²), but that was reduced after an interim safety analysis. The lower dosage “delivered 56 percent more chemotherapy to the tumor than conventional paclitaxel,” researchers said.

The primary endpoint was pCR, which serves as a surrogate marker for long-term efficacy.

Overall, 265 patients reported serious adverse events, including 146 patients in the Abraxane arm and 119 in the paclitaxel group. Four patients died on the study, with three deaths on the Abraxane arm (accident at home, multiorgan failure, sepsis) and one death on the paclitaxel arm (cardiac decompensation).

More patients in the Abraxane group discontinued treatment due to toxicities compared with the paclitaxel group (17 percent vs 6 percent), investigators said. However, there were fewer instances of local disease progression with Abraxane as opposed to paclitaxel (1.7 percent vs 5 percent).

Other investigators said in the GBG statement that the advantage with Abraxane held true among subgroups.

“We observed the superior effect of nab-paclitaxel in patients with triple-negative disease, 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,” said Sibylle Loibl, co-chair of the GBG, in the group’s statement.

The GBG disclosed that Celgene, which manufactures Abraxane, and Roche supported the GeparSepto study with unrestricted grants and the provision of medication.