Cancer Res Treat.  2018 Oct;50(4):1226-1237. 10.4143/crt.2017.446.

Safety Results and Analysis of Eribulin Efficacy according to Previous Microtubules-Inhibitors Sensitivity in the French Prospective Expanded Access Program for Heavily Pre-treated Metastatic Breast Cancer

• Sabatier R
• Diéras V
• Pivot X
• Brain E
• Roché H
• Extra JM
• Monneur A
• Provansal
• Tarpin C
• Bertucci F
• Viens P
• Zemmour C
• Gonçalves A

• KMID: 2424795
• DOI: http://doi.org/10.4143/crt.2017.446

Abstract

PURPOSE
Eribulin is approved for advanced breast cancers refractory to anthracyclines and taxanes. Efficacy according to sensitivity to previous therapies has been poorly explored.
MATERIALS AND METHODS
Safety data were collected prospectively and we retrospectively collected efficacy data from the five French centres that participated in the Eribulin E7389-G000-398 expanded access program. Our main objectives were exploration of safety and analysis of eribulin efficacy (progression-free survival [PFS] and overall survival [OS]) according to sensitivity to the last microtubule-inhibiting agent administered.
RESULTS
Median eribulin treatment duration was 3.3 months for the 250 patients included in this prospective single-arm study. Two hundreds and thirty-nine patients (95.6%) experienced an adverse event (AE) related to treatment including 129 (51.6%) with grade ≥ 3 AEs. The most frequently observed toxicities were cytopenias (59.6% of included patients), gastro-intestinal disorders (59.2%), and asthenia (56.4%). The most frequent grade 3-4 AE was neutropenia (37.2% with 4.8% febrile neutropenia). Median PFS and OS were 4.6 and 11.8 months, respectively. Patients classified as responders to the last microtubule-inhibiting therapy had a longer OS (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.51 to 0.94; p=0.017), and tended to display a better PFS (HR, 0.78; 95% CI, 0.58 to 1.04; p=0.086). OS improvement was still significant in multivariate analysis (adjusted HR, 0.53; 95% CI, 0.35 to 0.79; p=0.002).
CONCLUSION
This work based on a prospective study suggests that identification of patients likely to be more sensitive to eribulin could be based on their previous response to microtubules inhibitors.

Keyword

Metastatic breast cancer; Eribulin; Safety; Survival; Microtubule inhibition

MeSH Terms

Anthracyclines
Asthenia
Breast Neoplasms*
Breast*
Humans
Microtubules
Multivariate Analysis
Neutropenia
Prospective Studies*
Retrospective Studies
Taxoids
Anthracyclines
Taxoids

Figure

• 

  Fig. 1. CONSORT flow diagram. a)Safety data were prospectively collected, b)Efficacy data were retrospectively collected.

• 

  Fig. 2. Kaplan-Meier curves for the whole population (n=246). (A) Progression-free survival. (B) Overall survival. The efficacy population was defined as the group of subjects for whom at least one radiological assessment was available, even if they did not complete one cycle of treatment. One-year and 5-year progression-free survival were 14% and 0%, respectively. One-year overall survival was 48% and 5-year overall survival was 5%.

• 

  Fig. 3. Kaplan-Meier curves according to response to the last microtubule-inhibiting agent. (A) Progression-free survival. (B) Overall survival. The efficacy population was defined as the group of subjects for whom at least one radiological assessment was available, even if they did not complete one cycle of treatment.

Reference

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