Abstract OT1-01-05: PAINTER: Evaluation of eribulin tolerability and correlation between a set of polymorphisms and neuropathy in patients with metastatic breast cancer
Authors: La Verde N , Moretti A , Damia G , Paternò E , Santini D , Garrone O , Fabi A , Ciccarese M , Cretella E , Torri V , Generali D , Grasso D , Puglisi F , Collovà E , Roila F , Bertolini A , Barni S , Vici P , Luigi C , Scandurra G , Bramati A , Dazzani MC , Farina G 
Published: March 2017

Abstract
BACKGROUND Eribulin is a synthetic analogue of halichondrin B which inhibits microtubule dynamics. It has been approved in Europe for the treatment of locally advanced or metastatic breast cancer (mBC) progressed after at least two chemotherapy regimens for advanced disease. The most common adverse events (AEs) were fatigue, neutropenia and peripheral neuropathy, which occurs with an incidence ranging from 13.9% to 35%. It was severe only in a small proportion of patients, suggesting an individual susceptibility. The neurotoxicity mechanisms associated with microtubulin interfering agents have not been fully defined. Few studies reported an association between some SNPs (Single Nucleotide Polymorphisms) and microtubulin interfering agents-induced neuropathy, mainly taxanes. As the use of Eribulin becomes more widespread, a better knowledge of its safety profile, outside of clinical trials, is warranted. Given that Eribulin toxicity can result in treatment discontinuation, the ability to anticipate which patients will experience severe toxicity could allow for either early intervention or even possibly for prophylactic therapy, or for a better selection of patients eligible for treatment.
METHODS This is a multicenter, interventional, single-arm, phase IV study. The primary objective is the evaluation of the safety and tolerability profile of Eribulin in an unselected population of patients with mBC. Secondary objectives are the description of compliance to treatment and efficacy.
ENDPOINTS
•Incidence, time of onset, severity and duration of all AEs experienced during treatment with Eribulin, especially the most common reported in previous studies but also other possible unexpected toxicities.
•Association between a set of selected SNPs and the onset of any grade peripheral neuropathy. Specifically, 15 SNPs located in genes involved in microtubule dynamics or resulted from genome wide association studies, will be analyzed.
•Evaluation of quality of life during treatment using validated questionnaires.
•Assessment of dose intensity and dose schedule maintenance.
•DOT (Duration Of Treatment) and OS (Overall Survival).
STATISTICAL METHODS Summary statistics will be used in order to describe patient characteristics. Safety endpoints will be estimated by means of absolute and relative frequencies and associated 95%CI. The relationship between baseline variables and the risk of severe toxicity, as well as the relationship between SNPs and risk of neuropathy will be described by means of contingency tables and their association with outcome will be assessed by χ2 test of Mantel-Haenzel and a logistic regression model. DOT and OS will be described using Kaplan-Meier curves. A sample size of 200 patients will also allow us to get a good fitting for statistical analysis of the relationship between primary endpoint and not more than 10 factors. Regarding the relationship between SNPs and risk of neuropathy it will be feasible to screen for association about 10-15 SNPs, with known prevalence &gt;15%.
PRESENT ACCRUAL AND TARGET ACCRUAL 98 of 200 patients were enrolled until 18/05/2016. Target accrual is open for 200 patients.
CONTACT INFORMATION Nicla La Verde: nicla.laverde@asst-fbf-sacco.it.
Citation Format: La Verde N, Moretti A, Damia G, Paternò E, Santini D, Garrone O, Fabi A, Ciccarese M, Cretella E, Torri V, Generali D, Grasso D, Puglisi F, Collovà E, Roila F, Bertolini A, Barni S, Vici P, Luigi C, Scandurra G, Bramati A, Dazzani MC, Farina G. PAINTER: Evaluation of eribulin tolerability and correlation between a set of polymorphisms and neuropathy in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-01-05.