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)

Autor: Alba A. Brandes, Claudio Zamagni, Andrea Rocca, Renata Todeschini, Daniela Boggiani, Stefania Gori, Luigi Cavanna, Alessia Caldara, Federica Villa, Filippo Montemurro, Antonino Musolino, Federico Piacentini, A. Ardizzoni, Antonio Frassoldati, Luigi Boni, Jennifer Foglietta, R. Berardi, Beatrice Bortesi, Nadia Naldi, Benedetta Pellegrino, Michele Tognetto, Alessio Schirone
Přispěvatelé: Pellegrino B., Cavanna L., Boggiani D., Zamagni C., Frassoldati A., Schirone A., Caldara A., Rocca A., Gori S., Piacentini F., Berardi R., Brandes A.A., Foglietta J., Villa F., Todeschini R., Tognetto M., Naldi N., Bortesi B., Montemurro F., Ardizzoni A., Boni L., Musolino A., Pellegrino, B, Cavanna, L, Boggiani, D, Zamagni, C, Frassoldati, A, Schirone, A, Caldara, A, Rocca, A, Gori, S, Piacentini, F, Berardi, R, Brandes, A A, Foglietta, J, Villa, F, Todeschini, R, Tognetto, M, Naldi, N, Bortesi, B, Montemurro, F, Ardizzoni, A, Boni, L, Musolino, A
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Oncology
Cancer Research
medicine.medical_specialty
Phase II study
Phases of clinical research
Triple Negative Breast Neoplasms
Neutropenia
breast cancer
TNBC
eribulin
gemcitabine
metastatic
pharmacogenetics
Phase II study
locally advanced or metastatic triple negative breast cancer
ERIGE trial
GOIRC
Deoxycytidine
NO
chemistry.chemical_compound
Breast cancer
GOIRC
breast cancer
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Clinical endpoint
Humans
Furan
Prospective Studies
Furans
eribulin
Triple-negative breast cancer
Original Research
pharmacogenetics
Antineoplastic Combined Chemotherapy Protocol
business.industry
locally advanced or metastatic triple negative breast cancer
Pharmacogenetic
Microfilament Proteins
gemcitabine
Ketones
Microfilament Protein
medicine.disease
Ketone
Gemcitabine
metastatic
Regimen
Prospective Studie
chemistry
Female
business
TNBC
Eribulin
medicine.drug
ERIGE trial
Human
Zdroj: ESMO Open
Popis: 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.
Highlights • Eribulin plus gemcitabine showed a remarkable best ORR of 37.3% and a clinical benefit rate of 48.8%. • The most common grade 3/4 toxicities were liver toxicity and neutropenia without febrile neutropenia. • The study regimen partially lost its efficacy in patients harboring BRCA1/2 pathogenic variants. • SNPs in CYP3A4 and FGD4 genes were associated with increased risk of liver toxicity. • Three different SNPs in CDA∗2, RRM1, and CYP2C8 genes were significantly associated with poorer OS.
Databáze: OpenAIRE
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