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Two open-label, single arm, non-randomized phase II studies of irinotecan for the treatment of metastatic breast cancer in patients with increased copy number of the topoisomerase I gene

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Kümler, Iben ; Balslev, Eva ; Stenvang, Jan ; Brünner, Nils ; Ejlertsen, Bent ; Jakobsen, Erik Hugger ; Nielsen, Dorte Lisbet. / Two open-label, single arm, non-randomized phase II studies of irinotecan for the treatment of metastatic breast cancer in patients with increased copy number of the topoisomerase I gene. I: BMC Cancer. 2019 ; Bind 19, Nr. 1. s. 573.

Bibtex

@article{db0f76438bc34dca92c2e8915928f976,
title = "Two open-label, single arm, non-randomized phase II studies of irinotecan for the treatment of metastatic breast cancer in patients with increased copy number of the topoisomerase I gene",
abstract = "BACKGROUND: Treatment options in metastatic breast cancer are limited. New therapies preferable with predictive biomarkers are needed. The aim of these trials was to investigate if gene copy number of the topoisomerase 1 gene was predictive of response to the topoisomerase inhibitor irinotecan.METHODS: Two open-label, single-arm phase II studies including HER2 positive and negative patients were conducted. Patients were eligible for inclusion if the primary tumor or a metastatic lesion had increased expression of the topoisomerase 1 gene defined as a TOP1 gene copy number of ≥4 or a TOP1/CEN20 ratio of ≥2. Patients were treated with irinotecan +/- trastuzumab weekly for 4 weeks following 2 weeks break, until progression or unacceptable toxicities. Evaluation scans were performed every 6 weeks. Primary endpoint was clinical benefit rate defined as the fraction of patients with stable disease for ≥4 months.RESULTS: The pre-planned number of 18 patients in each trial was not reached, thus no formal statistical analysis could be performed. Nine patients with HER2 negative disease and three patients with HER2 positive disease were included. Three patients obtained a partial remission and two patients had SD.CONCLUSIONS: The trials did not include the planned number of patients. No association between gene copy number of the topoisomerase 1 gene and response to irinotecan could be proved, however a clinical benefit was found in 5/12 patients and in 2/3 patients with HER2 positive disease. This could call for further investigation of the drug in the metastatic setting, especially in HER2 positive BC.TRIAL REGISTRATION: Eudract registration numbers 2012-002348-26 and 2012-002347-23 . Registration date August 20th 2012.",
keywords = "Aged, Antineoplastic Agents/therapeutic use, Biomarkers, Pharmacological, Breast Neoplasms/diagnosis, DNA Topoisomerases, Type I/genetics, Drug Therapy, Combination, Female, Gene Dosage, Humans, Irinotecan/therapeutic use, Middle Aged, Predictive Value of Tests, Prognosis, Receptor, ErbB-2/metabolism, Topoisomerase I Inhibitors/therapeutic use, Trastuzumab/therapeutic use, Treatment Outcome",
author = "Iben K{\"u}mler and Eva Balslev and Jan Stenvang and Nils Br{\"u}nner and Bent Ejlertsen and Jakobsen, {Erik Hugger} and Nielsen, {Dorte Lisbet}",
year = "2019",
month = "6",
day = "13",
doi = "10.1186/s12885-019-5788-9",
language = "English",
volume = "19",
pages = "573",
journal = "B M C Cancer",
issn = "1471-2407",
publisher = "BioMed Central Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - Two open-label, single arm, non-randomized phase II studies of irinotecan for the treatment of metastatic breast cancer in patients with increased copy number of the topoisomerase I gene

AU - Kümler, Iben

AU - Balslev, Eva

AU - Stenvang, Jan

AU - Brünner, Nils

AU - Ejlertsen, Bent

AU - Jakobsen, Erik Hugger

AU - Nielsen, Dorte Lisbet

PY - 2019/6/13

Y1 - 2019/6/13

N2 - BACKGROUND: Treatment options in metastatic breast cancer are limited. New therapies preferable with predictive biomarkers are needed. The aim of these trials was to investigate if gene copy number of the topoisomerase 1 gene was predictive of response to the topoisomerase inhibitor irinotecan.METHODS: Two open-label, single-arm phase II studies including HER2 positive and negative patients were conducted. Patients were eligible for inclusion if the primary tumor or a metastatic lesion had increased expression of the topoisomerase 1 gene defined as a TOP1 gene copy number of ≥4 or a TOP1/CEN20 ratio of ≥2. Patients were treated with irinotecan +/- trastuzumab weekly for 4 weeks following 2 weeks break, until progression or unacceptable toxicities. Evaluation scans were performed every 6 weeks. Primary endpoint was clinical benefit rate defined as the fraction of patients with stable disease for ≥4 months.RESULTS: The pre-planned number of 18 patients in each trial was not reached, thus no formal statistical analysis could be performed. Nine patients with HER2 negative disease and three patients with HER2 positive disease were included. Three patients obtained a partial remission and two patients had SD.CONCLUSIONS: The trials did not include the planned number of patients. No association between gene copy number of the topoisomerase 1 gene and response to irinotecan could be proved, however a clinical benefit was found in 5/12 patients and in 2/3 patients with HER2 positive disease. This could call for further investigation of the drug in the metastatic setting, especially in HER2 positive BC.TRIAL REGISTRATION: Eudract registration numbers 2012-002348-26 and 2012-002347-23 . Registration date August 20th 2012.

AB - BACKGROUND: Treatment options in metastatic breast cancer are limited. New therapies preferable with predictive biomarkers are needed. The aim of these trials was to investigate if gene copy number of the topoisomerase 1 gene was predictive of response to the topoisomerase inhibitor irinotecan.METHODS: Two open-label, single-arm phase II studies including HER2 positive and negative patients were conducted. Patients were eligible for inclusion if the primary tumor or a metastatic lesion had increased expression of the topoisomerase 1 gene defined as a TOP1 gene copy number of ≥4 or a TOP1/CEN20 ratio of ≥2. Patients were treated with irinotecan +/- trastuzumab weekly for 4 weeks following 2 weeks break, until progression or unacceptable toxicities. Evaluation scans were performed every 6 weeks. Primary endpoint was clinical benefit rate defined as the fraction of patients with stable disease for ≥4 months.RESULTS: The pre-planned number of 18 patients in each trial was not reached, thus no formal statistical analysis could be performed. Nine patients with HER2 negative disease and three patients with HER2 positive disease were included. Three patients obtained a partial remission and two patients had SD.CONCLUSIONS: The trials did not include the planned number of patients. No association between gene copy number of the topoisomerase 1 gene and response to irinotecan could be proved, however a clinical benefit was found in 5/12 patients and in 2/3 patients with HER2 positive disease. This could call for further investigation of the drug in the metastatic setting, especially in HER2 positive BC.TRIAL REGISTRATION: Eudract registration numbers 2012-002348-26 and 2012-002347-23 . Registration date August 20th 2012.

KW - Aged

KW - Antineoplastic Agents/therapeutic use

KW - Biomarkers, Pharmacological

KW - Breast Neoplasms/diagnosis

KW - DNA Topoisomerases, Type I/genetics

KW - Drug Therapy, Combination

KW - Female

KW - Gene Dosage

KW - Humans

KW - Irinotecan/therapeutic use

KW - Middle Aged

KW - Predictive Value of Tests

KW - Prognosis

KW - Receptor, ErbB-2/metabolism

KW - Topoisomerase I Inhibitors/therapeutic use

KW - Trastuzumab/therapeutic use

KW - Treatment Outcome

U2 - 10.1186/s12885-019-5788-9

DO - 10.1186/s12885-019-5788-9

M3 - Journal article

VL - 19

SP - 573

JO - B M C Cancer

JF - B M C Cancer

SN - 1471-2407

IS - 1

ER -

ID: 59097298