P5-19-03: Albumin-Bound Paclitaxel (ab-pac) Versus Docetaxel for First-Line Treatment of Metastatic Breast Cancer (MBC): Overall Survival and Safety Analysis of a Randomized Phase II Trial

• Published in: Cancer research (Chicago, Ill.) Vol. 71; no. 24_Supplement; pp. P5 - P5-19-03
• Main Authors: Gradishar, WJ, Krasnojon, D, Cheporov, S, Makhson, AN, Manikhas, GM, Clawson, A, Bhar, P
• Format: Journal Article
• Language: English
• Published: 15-12-2011
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.SABCS11-P5-19-03

Abstract
Background
We previously reported the results of a phase II study evaluating the efficacy and safety of 3 different dosing regimens of ab-pac and docetaxel for the first-line treatment (Tx) of MBC (Gradishar et al. J Clin Oncol. 2009;27:3611–3619). Here, we report final overall survival (OS) and an analysis of safety and associated dose reductions (DRs).
Methods: Patients (pts; N = 300) with previously untreated MBC were randomized to 1 of 4 Tx arms (table). A step-down statistical approach was used for pairwise comparisons of Tx arms. The trial was powered for antitumor activity and safety.
Results: Tx arm C produced the longest OS (33.8 months) with an 11.6-month longer median OS vs arm B (HR 0.575; P = .008) and a 7.2-month longer median OS vs arm D (HR 0.688; P not statistically significant). OS data were consistent with previously reported investigator assessment of overall response rates and progression-free survival. Grade (gr) 4 neutropenia (np) was significantly less frequent in the ab-pac arms vs. the docetaxel arm (5-9% vs. 75%; P < .001). Febrile np occurred in 1% of each ab-pac arm vs 8% in the docetaxel arm. Rates of gr 3 sensory neuropathy (SN) were 21%, 9%, 22% and 12%, respectively, in arms A-D (P = .083). No gr 4 SN occurred. Median time to improvement to ≤ gr 2 SN was 20–22 days in the ab-pac arms vs 41 days in the docetaxel arm. Gr 3 fatigue occurred in 5, 0, 4, and 19% of pts in arms A-D, respectively. In arm C, best response was observed at cycle 2, whereas DRs due to toxicity occurred later, at cycle 4 (table). The percentage of pts dose reduced due to ≥ 1 Tx-related toxicity were 18%, 17%, 47%, and 28% in arms A-D. The median cycles at which DRs occurred were 7, 5, 4, and 3, respectively. Np and SN were the most common toxicities leading to DRs.
Conclusion: Ab-Pac 150 mg/m2 qw3/4 resulted in a 33.8-month OS, a longer OS than historically achieved with taxane monotherapy in MBC. Within the 150 mg/m2 ab-pac arm, best response occurred at cycle 2, whereas DRs due to toxicities occurred at later cycles. These data indicate that dosing ab-pac at 150 mg/m2 on a qw3/4 schedule may allow pts to achieve a clinical response before emergence of dose-limiting adverse events.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-19-03.