Nab-paclitaxel bests paclitaxel for high-risk breast cancer

SAN ANTONIO — Nab-paclitaxel improved DFS compared with paclitaxel in a cohort of patients with high-risk breast cancer, according to results of the prospective randomized phase 3 GeparSepto trial presented at the San Antonio Breast Cancer Symposium.

Earlier results from the GeparSepto study showed that the substitution of paclitaxel with nab-paclitaxel followed by epirubicin/cyclophosphamide as neoadjuvant chemotherapy improved pathological complete response from 29% to 38% (P < .001), especially among patients with triple-negative breast cancer (26% vs. 48%; P < .001).

A ndreas Schneeweiss, MD, of the National Center for Tumor Diseases at University Hospital, Heidelberg in Germany, conducted an analysis of this trial to determine whether there also was a survival benefit with nab-paclitaxel.

Researchers randomly assigned patients 80 mg/m² paclitaxel once a week for 12 weeks followed by four cycles of standard-dose epirubicin/cyclophosphamide every 3 weeks (n = 600), or 125 mg/m² nab-paclitaxel at the same dosing schedule with epirubicin/cyclophosphamide (n = 606).

Participants in the HER-2-positive group also received concomitant trastuzumab (Herceptin, Genentech; 8 mg/kg loading dose, 6 mg/kg thereafter) and pertuzumab (Perjeta, Genentech; 840 mg loading dose, 420 mg thereafter) every 3 weeks.

Pathologic complete response rate served as the primary endpoint in the initial analysis. Invasive DFS served as the secondary endpoint, along with OS overall and in certain subpopulations, quality-of-life parameters, cardiac toxicity, and detection of circulating tumor DNA at various points.

Median follow-up was 49 months (interquartile range, 44.6-52.9)
Three-year DFS rates improved in the nab-paclitaxel group compared with the paclitaxel group (87.1% vs. 80.7%; P = .0044). Schneeweiss highlighted that this was an absolute improvement of 6.4% for nab-paclitaxel.

By 4 years, the improvement in DFS for nab-paclitaxel had increased to 7.3% (83.5% vs. 76.2%).

Subtype analysis results showed a “pronounced” effect with nab-paclitaxel for triple-negative breast cancer in terms of 3-year DFS (83.1% vs. 73.4), Schneeweiss said. By 4 years, the difference in DFS was 78.7% for nab-paclitaxel and 68.6% for paclitaxel (P = .0694).

The improved DFS benefit with nab-paclitaxel was not as strong among patients with hormone receptor-positive, HER-2-negative disease (3 years, 86.3% vs. 78.6%; 4 years, 80.8% vs. 72.8%; P = .066).

Schneeweiss reported 133 deaths, but said OS data are not yet mature. “There is no difference in overall survival at this point,” he said.

However, the findings also suggested that patients who achieved a pathologic complete response also had favorable survival outcomes regardless of which therapy they received.

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“Patients without pathologic complete response have a significantly better DFS with nab-paclitaxel than with paclitaxel,” he said.

Other findings indicated that Ki67 was associated with benefit from nab-paclitaxel.

“The interaction with Ki67 suggests that nab-paclitaxel generates a long-term benefit, in particular, in tumors with lower proliferation,” Schneeweiss said.

“GeparSepto demonstrates a significantly improved DFS when patients received nab-paclitaxel instead of paclitaxel,” he concluded. – by Rob Volansky

Reference:

Schneeweiss A, et al. Abstract GS3-05. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.

Disclosures: Schneeweiss reports grants from Amgen, Celgene and Roche that are outside of the submitted work. Please see the abstract for all other authors’ relevant financial disclosures.