SAN ANTONIO—Nanoparticle albumin-bound paclitaxel (nab-paclitaxel or nP) is associated with improved pathologic complete response (pCR) rates compared to paclitaxel in taxane-first sequential taxane/anthracycline neoadjuvant therapy for breast cancer, according to findings from the randomized phase 3 GeparSepto trial (NCT01583426) that were presented at the 2014 San Antonio Breast Cancer Symposium.
“GeparSepto showed that the pCR rate is significantly higher with nab-paclitaxel compared [with] solvent-based paclitaxel given weekly before anthracycline-based chemotherapy,” reported lead study author Michael Untch, MD, of the HELIOS Hospital Berlin-Buch in Germany, and coauthors.
Anthracycline/taxane regimens are the neoadjuvant standard of care in breast cancer, the researchers noted. But reversing treatment to administer taxanes first, followed by anthracyclines, appears to yield higher pCR rates, the researchers noted, citing findings from a separate study recently published in The Lancet Oncology. Duel HER2 blockade has been shown to be “superior to trastuzumab alone,” they added.
nP is a solvent-free albumin-encapsulated formulation of paclitaxel, and might not only further improve pCR rates in patients with breast cancer receiving neoadjuvant treatment, but might also be associated with lower toxicity.
GeparSepto trial participants were randomly assigned to receive either nP (125 mg/m2) every week or paclitaxel (80 mg/ m2) every week for 12 weeks followed by 4 cycles of the anthracycline, epirubicin (90 mg/ m2), and cyclophosphamide (600 mg/m2) every 3 weeks, followed by surgery. For women with HER2+ tumors, trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks until surgery) and pertuzumab (840 mg absolute-dose loading dose followed by 420 mg every 3 weeks until surgery) were also administered throughout study treatment.
A total of 1,204 participants recruited between July 2012 and December 2013 were evaluable. Of these, 606 received nP.
The pCR rate (ypT0 ypN0: no evidence of tumor in the breast and negative axillary nodes) was 29% for patients in the paclitaxel group versus 38% for the nP group (odds ratio [OR]: 1.53; P<0.001), Dr. Untch reported. pCR was particularly impressive for triple-negative breast cancer (OR: 2.69, 95% CI: 1.62, 4.46; P<0.001), he emphasized.
“Baseline characteristics were well balanced,” Dr. Untch said. “The median age was 50 years in both groups (P/nP), median tumor size was 3 cm in each, 67% of each were HER2-negative, 69% of each group had Ki67 greater than 20%.”
Hematologic toxicities included anemia (any grade: 88.3% paclitaxel vs. 92.4% nP; P=0.019); neutropenia (any grade: 81.5% paclitaxel vs. 87.3% nP; P=0.007). The differences for both anemia and neutropenia was not statistically significant when only grade 3/4 adverse events (AEs) were considered, however. Nonhematological toxicities (any grade) were also more frequent in nP for diarrhea, rash, hand-foot syndrome, peripheral sensory neuropathy, and myalgia. Of these, only peripheral neuropathy was significantly more frequent for grade 3/4 AEs.
Discontinuation of taxane treatment was worse among women in the nP group (86% of paclitaxel-group participants completed treatment compared with 79% in the nP group; P<0.001), he reported. Reasons for taxane discontinuation included adverse events (6.2% for paclitaxel vs. 17% for nP) and disease progression (5% paclitaxel vs. 1.7% for nP).
“The primary study endpoint was reached,” Dr. Untch concluded. “Nab-paclitaxel significantly increased the pCR rate compared [with] paclitaxel. This effect was seen in all subgroups, especially in patients with triple-negative tumors.”
Long-term follow-up is required to determine if the improved pCR rate translates into improved survival rates, he cautioned.
The GeparSepto trial was financially supported by Celgene and Roche.
1. Untch M, Jackisch C, Schneeweiß A et al. S2-07. Presented at: San Antonio Breast Cancer Symposium 2014. Dec. 9-13, 2014; San Antonio, TX.
2. Earl HM, Vallier AL, Hiller L, et al. Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2×2 factorial randomised phase 3 trial. Lancet Oncol. 2014;15(2):201-212.