Abstract
Abstract
Background: Triple-negative breast cancer (TNBC) is an aggressive, poor-prognosis BC subtype characterized by a lack of estrogen receptor (ER), progesterone receptor (PgR), and HER2 overexpression. The taxanes are among the most effective agents in the treatment of BC, and nab-paclitaxel (nab-P), a non-solvent based taxane, has demonstrated favorable efficacy and safety profiles in metastatic BC (MBC). In combination with gemcitabine (gem) or carboplatin/bevacizumab (carbo/bev), nab-P has demonstrated high response rates as first-line treatment in metastatic TNBC (mTNBC). This phase 2/3 open-label, randomized trial (triple-negative Albumin-bound paclitaxel combination international treatment study [tnAcity]) will evaluate the efficacy and safety profiles of 2 nab-P combination regimens (with either gem or carbo) in addition to comparing the progression-free survival (PFS) of these 2 regimens with that of gem plus carbo as first-line treatment for mTNBC.
Methods: The phase 2 portion of the study will evaluate 240 patients (pts), randomized 1:1:1 (stratified by disease-free interval [DFI]: ≤ 1 y vs > 1 y) to receive nab-P 125 mg/m2 plus gem 1000 mg/m2 (arm A), nab-P 125 mg/m2 plus carbo area under the curve (AUC) 2 (arm B), or the control regimen of gem 1000 mg/m2 plus carbo AUC 2 (arm C) given on days 1 and 8 of a 21-day cycle. Eligibility criteria included: no prior cytotoxic therapy for metastatic disease; TNBC defined as ER and PgR expression < 1% by IHC and HER2 0 or 1 by IHC or 2+ by IHC but confirmed negative by FISH (FISH HER2/CEP17 ratio < 1.8 or average HER2 gene copy number of < 4 signals/nucleus); prior adjuvant or neoadjuvant anthracycline use unless contraindicated; measurable disease (RECIST v1.1), ECOG performance status ≤ 1; peripheral neuropathy grade < 2; and absence of brain metastases. Prior taxane therapy was permitted, provided it was completed > 12 months prior to study entry. The primary objective of the phase 2 portion is to identify the nab-P combination arm that will be evaluated in the phase 3 portion of the study. The primary endpoint of the phase 2 portion is PFS; secondary endpoints include overall response rate (ORR), percentage of pts who receive ≥ 6 cycles of treatment, overall survival (OS), and safety. In the phase 3 portion of the trial, 550 pts will be randomized 1:1 (stratified by DFI [≤ 1 y vs > 1 y] and prior taxane exposure) to the nab-P combination treatment arm (either arm A or B) selected from the phase 2 portion based on a ranking algorithm of 5 efficacy and safety endpoint parameters or to gem/carbo as described in the phase 2 segment. The primary endpoint of the phase 3 portion is PFS by independent radiologist assessment; secondary endpoints include ORR, OS, disease control rate, duration of response, and safety. Exploratory endpoints include circulating tumor cell enumeration, tumor biomarker assessment, quality of life, and healthcare economics. This design provides ≈ 90% power to detect a hazard ratio of 0.70 for PFS with a 2-sided 5% significance level, which represents a 43% improvement in median PFS by the nab-P experimental arm.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-1-11.