Paclitaxel injection concentrate for nanodispersion versus nab-paclitaxel in women with metastatic breast cancer: a multicenter, randomized, comparative phase II/III study

Abstract

Paclitaxel is widely used in the treatment of patients with metastatic breast cancer (MBC). Formulations of paclitaxel contain surfactants and solvents or albumin derived from human blood. The use of co-solvents such as polyoxyethylated castor oil is thought to contribute to toxicity profile and hypersensitivity reactions as well as leaching of plasticizers from polyvinyl chloride bags and infusion sets. Currently, nab-paclitaxel, an albumin-bound paclitaxel in nanometer range continues to be the preferred taxane formulation used in clinic. This study (CTRI/2010/091/001116) investigated the efficacy and tolerability of a polyoxyethylated castor oil- and albumin-free formulation of paclitaxel [paclitaxel injection concentrate for nanodispersion (PICN)] compared with nab-paclitaxel in women with refractory MBC. The current study was a multicenter, open-label, parallel-group, randomized, comparative phase II/III trial evaluating the efficacy and safety of PICN (260 mg/m2 [n = 64] and 295 mg/m2 [n = 58] every 3 weeks) compared with nab-paclitaxel (260 mg/m2 every 3 weeks [n = 58]) in women 18 and 70 years old with confirmed MBC. Overall response rate (ORR) was assessed with imaging every 2 cycles. An independent analysis of radiologic data was performed for evaluable patients. Progression-free survival (PFS) was a secondary efficacy measure. Independent radiologist-assessed ORRs in the evaluable population of women aged ≥70 years were 35, 49, and 43 % in the PICN 260 mg/m2, PICN 295 mg/m2, and nab-paclitaxel 260 mg/m2 arms, respectively. Median PFS in the evaluable population was 23, 35, and 34 weeks in the PICN 260 mg/m2, PICN 295 mg/m2, and nab-paclitaxel 260 mg/m2 arms, respectively. Adverse events occurred in similar proportions of patients across treatment arms. Hypersensitivity reactions were not frequently observed with the clinical use of PICN across the treatment cohorts. In women with metastatic breast cancer, PICN at 260 and 295 mg/m2 every 3 weeks was effective and well tolerated and showed similar tolerability compared with nab-paclitaxel 260 mg/m2 every 3 weeks. Statistically, significant differences were not observed in the PICN and nab-paclitaxel treatment arms for radiologist-assessed ORR or median PFS. The novel paclitaxel formulation, PICN, offers apart from efficacy, potential safety advantage of decreased use of corticosteroid pretreatment and the absence of the risk of transmission of blood product-borne disease.

<p>Improvement of Paclitaxel-Associated Adverse Reactions (ADRs) via the Use of Nano-Based Drug Delivery Systems: A Systematic Review and Network Meta-Analysis</p>

“…After observation of the eligibility criteria, 19 primary articles were selected, including 16 articles in English and three articles in Chinese (Figure 1). 5,18,20,21,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] These articles comprised a total of 5787 participants and six paclitaxel formulations including solvent-based paclitaxel, Nab-P, Lip-P, PM-P, PPX, and PICN. The regimens and dose characteristics of the included studies are presented in Table 2.…”

“…A phase I study showed that the MTD of PICN is 325 mg/m 2 and that its administration did not cause hypersensitivity reactions. 21 Most studies investigating nanoparticle paclitaxel delivery were performed using head-to-head comparative studies to investigate effectiveness; however safety profiles were not considered. The aim of this study was to compare the ADRs of various paclitaxel formulas by collecting and analyzing randomized controlled trial (RCTs).…”

Efficacy and safety of Nab-paclitaxel in breast cancer: a meta-analysis

“…A total of eight studies [10][11][12][13][14][15][16][17] which fulfilled our criteria were included in this study. We did not found any difference in efficacy of nab-paclitaxel over paclitaxel (12 months progression free survival-RR FE = 0.86, 95%CI= 0.77-0.97, p= 0.02, I 2 = 25.07%; 24 months progression free survival-RR FE = 0.86, 95% CI= 0.64-1.16, p= 0.34, I 2 = 0%; and 3 years survival-RR FE = 1.20, 95%CI= 0.92-1.56, p= 0.16, I 2 = 37.55%) (Figure 1).…”

A Systematic Review and Meta-Analysis of Nab-Paclitaxel Mono-Chemotherapy for Metastatic Breast Cancer.

“…We ultimately identified 22 independent studies published between March 2005 and March 2020 [9,10,12,13,16,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37]. A flow chart representing selection of studies is shown in Figure 1 Table 1.…”