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Rigshospitalet - a part of Copenhagen University Hospital

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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  • Iben Kümler
  • Eva Balslev
  • Jan Stenvang
  • Nils Brünner
  • Bent Ejlertsen
  • Erik Hugger Jakobsen
  • Dorte Lisbet Nielsen
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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.

Original languageEnglish
JournalBMC Cancer
Issue number1
Pages (from-to)573
Publication statusPublished - 13 Jun 2019

    Research areas

  • 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

ID: 59097298