Metastatic breast cancer (MBC) is an incurable disease and its treatment focuses on prolonging patients (pts) overall survival (OS) and improving their quality of life. eribulin is a microtubule inhibitor that increases OS in pre-treated MBC pts. Its common adverse events (AEs) are asthenia, neutropenia and peripheral neuropathy (PN).
The PAINTER is a single arm, phase IV study, aimed at surveying eribulin tolerability in MBC pts. Secondary objectives were to explore incidence and severity of PN, its association with genetic polymorphisms, and the description of treatment efficacy and safety. Genomic DNA was isolated from blood samples and 15 Single Nucleotide Polymorphisms (SNPs) were genotyped by Taqman specific assays. The associations between PN and SNPs were evaluated by Fisher exact test.
From May 2014 to June 2018 180 pts were enrolled from 20 Italian centers; 170 were evaluable for efficacy and toxicity and 159 for polymorphisms analysis. Median age was 60 years, biological subtypes were luminal type (64.7%), Her2 positive (18.3%) and triple negative (17%). Pts were pretreated with a median of 5 lines for MBC. With a median follow up of 15.4 months, a median number of eribulin cycles of 4.5 (minimum-maximum 1-23), median overall survival was 12 months. 48.8% of pts experienced dose reduction, mainly for neutropenia (23.9%) and liver injury (12%). 65 pts (38.2%) reported at least one severe toxicity. Neutropenia and neurotoxicity were the most frequent severe AEs (15.3% and 14.7% respectively); other toxicities were osteo-muscular, abdominal or tumor site pain (19.4%), liver injury (6.6%), pulmonary toxicity (6.5%) and dermatological (3.6%), Among the 15 evaluated SNPs, an association with PN was found for rs2233335 and rs7214723.
Eribulin is a well-tolerated treatment in MBC. Schedule and dosage modifications were common, but toxicity rarely led to treatment discontinuation. SNPs rs2233335 (G/T and T/T) in NDRG1 gene and rs7214723 (CC and CT) in CAMKK1 gene were associated with PN. These findings, if validated, could allow a tailored eribulin treatment in cancer patients.
Trial registration: ClinicalTrials.gov ID: NCT02864030