Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer patients: prospective evaluation of activity, safety, and quality of life

Abstract

BackgroundA prospective, multicenter trial was undertaken to assess the activity, safety, and quality of life of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer (MBC).Patients and methodsFifty-two women with HER2-negative MBC who were candidates for second-line chemotherapy for the metastatic disease were enrolled and treated at three centers in Northern Italy. All patients had previously received taxane-based chemotherapy in the adjuvant or first-line metastatic setting. Single-agent nab-paclitaxel was given at the dose of 260 mg/m2 as a 30-minute intravenous infusion on day 1 each treatment cycle, which lasted 3 weeks, in the outpatient setting. No steroid or antihistamine premedication was provided. Treatment was stopped for documented disease progression, unacceptable toxicity, or patient refusal.ResultsAll of the enrolled patients were evaluable for the study endpoints. The objective response rate was 48% (95% CI, 31.5%–61.3%) and included complete responses from 13.5%. Disease stabilization was obtained in 19 patients and lasted >6 months in 15 of them; the overall clinical benefit rate was 77%. The median time to response was 70 days (range 52–86 days). The median progression-free survival time was 8.9 months (95% CI, 8.0–11.6 months, range 5–21+ months). The median overall survival point has not yet been reached. Toxicities were expected and manageable with good patient compliance and preserved quality of life in patients given long-term treatment.ConclusionOur results showed that single-agent nab-paclitaxel 260 mg/m2 every 3 weeks is an effective and well tolerated regimen as second-line chemotherapy in HER2-negative, taxane-pretreated MBC patients, and that it produced interesting values of objective response rate and progression-free survival without the concern of significant toxicity. Specifically, the present study shows that such a regimen is a valid therapeutic option for that ‘difficult to treat’ patient population represented by women who at the time of disease relapse have already received the most active agents in the adjuvant and/or metastatic setting (ie, conventional taxanes).

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

“…The hereby reviewed data confirm that sensorial neuropathy occurs late in the course of treatment with both the qw and q3w schedules, also in taxane-pretreated patients, and adequate management by dose reductions or treatment delays allows to maintain an adequate dose-intensity of the drug [Gradishar et al 2005[Gradishar et al , 2009Blum et al 2007;Von Minckwitz et al 2013;Palumbo et al 2015aPalumbo et al , 2015b.…”

“…Similarly, a strong association between caveolin-1 expression and breast carcinomas with a basal-like phenotype has been reported, suggesting that the utilization of the gp60/caveolin-1 pathway as a means to deliver cytotoxic therapy may be particularly lucrative in some breast cancer subtypes [Pinilla et al 2006;Savage et al 2007] and that patients with higher caveolin-1 expression, such as those with a basallike phenotype, may derive greater benefit from nab-paclitaxel [Altundag et al 2006]. On the other hand, retrospective and real-life data showed a significantly higher ORR in patients with visceral-dominant metastases treated with nab-paclitaxel compared with solvent-based paclitaxel [O'Shaughnessy et al 2013;Palumbo et al 2015aPalumbo et al , 2015b. Thus, disease-related factors such as visceral-dominant metastases may be clinical predictive markers of treatment response.…”

Comparison of the Therapeutic Efficacy of the Early and the Delayed Use of Vinorelbine-Based Regimens for Patients with Advanced Breast Cancer

“…Many studies have shown that single-agent nab-paclitaxel 260 mg/m 2 every 3 weeks is an effective and well-tolerated regimen as second-line chemotherapy in HER2-negative, taxane-pretreated MBC, and that it produced interesting values of ORR and PFS without the concern of significant toxicity [35]. For example, a prospective, multicenter trial was conducted to assess the activity and safety of nab-paclitaxel as second-line chemotherapy in HER2-negative, taxane-pretreated MBC [36]. The ORR was 48%, and the overall CBR was 77%.…”

Efficacy and Safety of Eribulin in Taxane-Refractory Patients in the “Real World”

“…Vinorelbine has been widely employed in pretreated breast cancer, either in its intra-venous or oral formulation, yielding response rates ranging from 10% to 35% [18,19]. Additional agents include nab-paclitaxel, which in two phase II trials yielded a response rate of 15% and 48% respectively in taxane pre-treated patients [20,21]. Ixabepilone, was quite active in heavily pre-treated patients, with a 18.5% response rate, however, because of its relevant neurotoxicity, observed in 63% of the patients, was not approved by EMA [22][23][24].…”