Correlation between NDRG1 gene polymorphism and neuropathy (N) in metastatic breast cancer (MBC) patients (pts) enrolled in the PAINTER study (Polymorphism And INcidence of Toxicity in ERibulin treatment).

Authors

null

Nicla Maria La Verde

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

Organizations

Department of Oncology ASST Fatebenefratelli Sacco P.O. Fatebenefratelli, Milan, Italy, Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy, Breast Unit Medical Oncology S. Croce and Carle Teaching Hospital, Cuneo, Italy, Università Campus Biomedico, Rome, Italy, Division of Medical Oncology, “Regina Elena” National Cancer Institute, Rome, Italy, Vito Fazzi Hospital, Lecce, Italy, Istituti Osp.di Cremona, Cremona, Italy, Azienda Ospedaliera S. Maria, Terni, Italy, Department of Oncology - ASUI Udine, Academic Hospital, Udine, Italy, Udine, Italy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, Comprensorio Sanitario Oncologia, Bolzano, Italy, Oncologia Medica Ospedale per le Emergenze Cannizzaro, Catania, Italy, University of Florence, Florence, Italy, S.C. Oncologia - ASST Valtellina e Alto Lario, Sondrio, Italy, Oncology-Hematology Department, Hospital of Piacenza, Piacenza, Italy, UOC Oncologia, Ospedale Macerata, Macerata, Italy, Unit of Statistics, Laboratory of Methodology for Clinical Research Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy, Dept.of Oncology ASST Fatebenefratelli Sacco, P.O. Fatebenfratelli, Milan, Italy, Dept. of Oncology ASST Fatebenefratelli - Sacco Hospital, P.O. Fatebenefratelli, Milan, Italy

Research Funding

Pharmaceutical/Biotech Company

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/G4/24 (16.7)20 (22.2)1 (3.7)1 (7.1)2 (50.0)
G/T14/60 (23.3)46 (51.1)10 (37.0)3 (21.4)1 (25.0)
T/T27/51 (52.94)24 (26.7)16 (59.3)10 (71.4)1 (25.0)

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Developmental Therapeutics and Tumor Biology (Nonimmuno)

Track

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Sub Track

Pharmacology/Pharmacodynamics/Pharmacogenetics

Clinical Trial Registration Number

NCT02864030

Citation

J Clin Oncol 37, 2019 (suppl; abstr 3116)

DOI

10.1200/JCO.2019.37.15_suppl.3116

Abstract #

3116

Poster Bd #

108

Abstract Disclosures

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