In the phase III GeparSepto-GBG 69 trial, reported in The Lancet Oncology by Untch et al, neoadjuvant nab-paclitaxel (Abraxane) improved pathologic complete response rate vs conventional solvent-based paclitaxel in women with early-stage breast cancer.
In the open-label trial, 1,206 women (the number who started treatment) from 69 German sites were randomly assigned between July 2012 and December 2013 to receive nab-paclitaxel (n = 606) or solvent-based paclitaxel (n = 600). Treatment consisted of 12 weeks of nab-paclitaxel at 150 mg/m2 or, after study amendment, 125 mg/m2 on days 1, 8, and 15 for four 3-week cycles or solvent-based paclitaxel at 80 mg/m2 on days 1, 8, and 15 for four 3-week cycles. Taxane treatment was followed in both groups by epirubicin at 90 mg/m2 plus cyclophosphamide at 600 mg/m2 on day 1 for four 3-week cycles. Patients with HER2-positive disease received concurrent trastuzumab (Herceptin) at 6 mg/kg after a loading dose of 8 mg/kg and pertuzumab (Perjeta) at 420 mg after a loading dose 840 mg on day 1 of every 3-week cycle.
The nab-paclitaxel dose was reduced after enrollment of 464 participants due to increased treatment discontinuation and sensory neuropathy in the treatment group. The primary endpoint was pathologic complete response (ypT0 ypN0) in all patients who started treatment.
Pathologic Complete Response
Pathologic complete response was observed in 38% (95% confidence interval [CI] = 35%–42%) of the nab-paclitaxel group vs 29% (95% CI = 25%–33%) of the solvent-based paclitaxel group (odds ratio [OR] = 1.53, P = .00065). In analysis by biologic subtype, a significant advantage of nab-paclitaxel was observed only among the 276 patients with triple-negative disease (OR = 2.61, P = .00020).
Grade 3 or 4 anemia (2% vs 1%, P = .048) and grade 3 or 4 peripheral sensory neuropathy (10% overall, including 15% at the higher dose and 8% at the lower dose, vs 3%, P < .001) were significantly more common in the nab-paclitaxel group. Serious adverse events occurred in 26% vs 21% of patients (P = .057). Three deaths occurred during treatment in the nab-paclitaxel group, with all occurring during epirubicin/cyclophosphamide treatment (due to sepsis, diarrhea, and accident); one death occurred in the solvent-based paclitaxel group during treatment, occurring during paclitaxel treatment (due to cardiac failure).
The investigators concluded: “Substituting solvent-based paclitaxel with nab-paclitaxel significantly increases the proportion of patients achieving a pathological complete response rate after anthracycline-based chemotherapy. These results might lead to an exchange of the preferred taxane, solvent-based paclitaxel, for nab-paclitaxel in therapy for primary breast cancer.”
The study was funded by Celgene and Roche.
Sibylle Loibl, MD, of the German Breast Group, Neu-Isenburg, is the corresponding author of The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.