Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer (ERIGE trial). Clinical and pharmacogenetic results on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC)

ESMO Open

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B. Pellegrino¹  L. Cavanna⁴  D. Boggiani¹  C. Zamagni⁵  A. Frassoldati²  A. Schirone⁶  A. Caldara⁷  A. Rocca⁸  S. Gori⁹  F. Piacentini^1,10  R. Berardi^1,11  A.A. Brandes^1,12  J. Foglietta^1,13  F. Villa^1,14  R. Todeschini²  M. Tognetto^1,15  N. Naldi¹  B. Bortesi¹  F. Montemurro^1,16  A. Ardizzoni^1,15  L. Boni^1,17  A. Musolino¹ 

[1] Medical Oncology and Breast Unit, University Hospital of Parma;Italian Oncology Group for Clinical Research;Department of Medicine and Surgery, University of Parma;Hospital of Piacenza;SSD Oncologia Medica Addarii, Policlinico S.Orsola-Malpighi;Medical Oncology Unit, University Hospital of Ferrara;Medical Oncology Unit, Ospedale Santa Chiara;Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori;Sacro Cuore-Don Calabria Hospital;Medical Oncology Unit, University Hospital of Modena;Ancona University Hospital;Department of Medical Oncology;Hospital of Perugia;Hospital of Lecco;Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna;Multidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute;Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino

关键词: breast cancer;    TNBC;    eribulin;    gemcitabine;    metastatic;    pharmacogenetics;   

DOI  :  10.1016/j.esmoop.2020.100019

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, particularly in triple negative breast cancer (TNBC) characterized by high cell proliferation, aggressive behavior, and chemo-resistance.Patients and methods This is an open-label, multicenter phase II study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on days 1 and 8 of a 21-day cycle as either first- or second-line treatment of locally advanced or metastatic TNBC. The primary endpoint was the objective response for evaluable patients. A prospective, molecular correlative study was carried out to assess the role of germinal BRCA pathogenic variants and single nucleotide polymorphisms (SNPs) in predicting efficacy and toxicity of the combination regimen.Results From July 2013 to September 2016, 83 evaluable patients were enrolled. They received a median number of six cycles of treatment. An overall response rate (ORR) of 37.3% (31 patients) was observed, with a complete response rate of 2.4% and a partial response rate of 34.9%; the clinical benefit rate was 48.8%. With a median follow-up of 28.8 months, the median response duration was 6.6 months, the median progression-free survival (PFS) was 5.1 months, and the median overall survival (OS) was 14.5 months. The most common grade 3-4 adverse events were aminotransferase elevation (in 25% of the patients) and neutropenia (in 23.8%). Women with BRCA1/2 pathogenic variants were associated with worse ORR, PFS, and OS than BRCA1/2 wild-type carriers. CYP3A4 and FGD4 SNPs were associated with increased risk of liver toxicity. Three different SNPs in CDA∗2, RRM1, and CYP2C8 genes were significantly associated with poorer OS.Conclusions The combination of eribulin and gemcitabine showed promising activity and a moderate toxicity profile in metastatic TNBC. BRCA status and pharmacogenetics tests may help identify patients with high probability of response with negligible toxicity.EudraCT number 2012-003505-10.

【 授权许可】

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