Department of Oncology ASST Fatebenefratelli Sacco P.O. Fatebenefratelli, Milan, Italy
Nicla Maria La Verde , Giovanna Damia , Ornella Garrone , Loretta D'Onofrio , Alessandra Fabi , Mariangela Ciccarese , Daniele Giulio Generali , Martina Nunzi , Elena Poletto , Paolo Pedrazzoli , Elisabetta Cretella , Giuseppa Scandurra , Icro Meattini , Alessandro Stefano Bertolini , Luigi Cavanna , Emanuela Romagnoli , Lorenzo Legramandi , Federica Guffanti , Barbara Bocci , Gabriella Farina
Background: MBC is an incurable disease and therefore treatment focuses mainly on prolonging pts survival and improving quality of life. Eribulin (E) is a microtubule inhibitor that increased overall survival in pretreated pts. E peripheral N is reported in 13.9-35% of cases. PAINTER main objective was to survey tolerability of E in real life in MBC, while secondary endpoints were to investigate the relationships between specific genetic polymorphisms and incidence and severity of peripheral N. Methods: This is a multicenter, interventional, single-arm, phase IV study, that enrolled pts who received E after taxanes and antracyclines (dose 1.4 mg/m2 day 1, 8 every 21 days). PAINTER study follow-up is still ongoing. Genomic DNA was isolated from whole blood samples (Maxwell whole blood DNA kit. Promega). 15 SNPs (Single Nucleotide Polymorphisms) were genotyped by Taqman specific assays. For SNPs analysis, we selected pts with avaliable clinical data and who completed E treatment. N was evaluated by medical examination. The associations between peripheral N (any grade) and the selected polymorphisms were evaluated with Fisher exact test. Results: From May 2014 to June 2018, 180 pts were enrolled in the PAINTER study from 20 Italian hospitals and 135 were analysed for the present report. Pts and tumor characteristics were as follow: median age 62 years (31-85), ductal carcinoma 78.5%, visceral disease 70.4%, luminal type 62.6%, Her2 positive 20.3%, triple negative 17.1%, previous median treatment lines for MBC 5 (0-18), previous N reported in 17.8% of pts (sensory 87.5%, motor 12.5%). N (all grades) were reported in 33.4% of patients (G3-G4: 3%). Among the selected SNPs, one allelic variant (rs2233335 G/G versus G/T or T/T) in NDRG1 gene had a statistically significant association with N (p 0.0010). Conclusions: The data reported demonstrate for the first time that the allelic variant rs2233335 (G/T and T/T) in NDRG1 gene correlates with E induced N. These data, if corroborated, will allow a tailored treatment with E. Clinical trial information: NCT02864030
rs2233335 Allelic variant | G1-2-3 Neurotoxicity n (%) | G0 n (%) | G1 n (%) | G2 n (%) | G3 n (%) |
---|---|---|---|---|---|
G/G | 4/24 (16.7) | 20 (22.2) | 1 (3.7) | 1 (7.1) | 2 (50.0) |
G/T | 14/60 (23.3) | 46 (51.1) | 10 (37.0) | 3 (21.4) | 1 (25.0) |
T/T | 27/51 (52.94) | 24 (26.7) | 16 (59.3) | 10 (71.4) | 1 (25.0) |
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