Final results of a phase II study of nab-paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer

Abstract

In order to examine the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-P) in combination with bevacizumab (B) and gemcitabine (G) for the first-line treatment of patients with HER2-negative metastatic breast cancer (MBC). In this single-center, open-label phase II trial, patients with HER2-negative MBC received gemcitabine 1500 mg/m(2), nab-paclitaxel 150 mg/m(2), and bevacizumab 10 mg/kg (each administered intravenously) on days 1 and 15 of a 28-day cycle. The primary end point was progression free survival (PFS); secondary end points were overall response rate (ORR), complete (CR) and partial (PR) response rates, clinical benefit (ORR + stable disease), overall survival (OS), and safety. Thirty patients were enrolled. One patient was ineligible and was not included in analysis. Median PFS was 10.4 months (95% CI: 5.6-15.2 months). ORR was 75.9%, comprising eight (27.6%) CRs and 14 (48.3%) PRs; five patients had stable disease (SD) and two patients (6.9%) had progressive disease (PD) as their best response. The clinical benefit rate was 93.1% (27/29) in the overall group and 84.6% in the triple-negative cohort (11/13). The 18-month survival rate was 77.2% (95% CI: 51.1-90.5%). Eight (27.6%) patients experienced grade 3 or 4 toxicity: grade 4 neutropenic fever (n = 1) and grade 3 infection (n = 6), leukopenia, thrombocytopenia, peripheral neuropathy, seizure, shortness of breath, hematuria, and cardiac tamponade (one each). First-line therapy with nab-P, B, and G demonstrated a median PFS of 10.4 months and a 75.9% ORR with acceptable toxicity; this novel combination warrants investigation in a randomized study.

A randomized controlled phase II trial of a novel composition of paclitaxel embedded into neutral and cationic lipids targeting tumor endothelial cells in advanced triple-negative breast cancer (TNBC)

“…During the first-line treatment of HER2-negative BC, combinations of bevacizumab and nab-paclitaxel achieved responses of 30%-46% and PFS of 7.7-9.2 months [25,26]. Addition of gemcitabine to this combination showed responses of 76%, PFS of 10.4 months, and OS of 18 months [27]. With PFS of 6.6 months and OS of 17.8 months on EndoTAG™-1/paclitaxel combination therapy, similar results were obtained in the present study for a comparable subgroup (TNBC, ECOG 0/1, and first-line), presumably representing the most promising patient population for vascular-targeting agents such as EndoTAG™-1.…”

Targeted chemotherapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in metastatic breast cancer: which benefit for which patients?

“…3. The available studies of nab-paclitaxel-containing regimens for metastatic TNBC demonstrate promising efficacy data, such as an ORR of 34-85% [Lobo et al 2010;Hamilton et al 2013;Rugo et al 2015], but future research is needed to answer questions as to the overall effectiveness and the ideal nab-paclitaxel regimen in this challenging setting. Subset analysis of randomized trials and recently reported realworld experiences also support the use of single-agent nab-paclitaxel for women with other disease features associated with poor prognostic factors, as visceral-dominant metastases and DFI of no less than 2 years.…”

“…To date, only one trial has been completed and published in which a TNBC-exclusive population was treated with nab-paclitaxel. [Lobo et al 2010]. Finally, a randomized phase III trial by the Cancer and Leukemia Group B (Trial CALGB 40502) compared qw paclitaxel 90 mg/m 2 given the first 3 of 4 weeks (qw3/4) plus bevacizumab 10 mg/kg every 2 weeks (q2w) versus nab-paclitaxel 150 mg/m 2 qw3/4 plus bevacizumab 10 mg/kg q2w or ixabepilone 16 mg/kg qw3/4 plus bevacizumab 10 mg/ kg q2w.…”

Cisplatin improves antitumor activity of weekly nab-paclitaxel in patients with metastatic breast cancer

“…22 Several trials adding other drugs to nab-paclitaxel have been conducted to further improve the efficacy, such as carboplatin, gemcitabine, bevacizumab, and herceptin. [23][24][25] On the basis of our knowledge, this is also the first trial showing that the already-strong antitumor activity of weekly nab-paclitaxel for MBC can be further increased by adding a chemotherapeutic agent.…”