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Breast Cancer Research and Treatment

, Volume 134, Issue 1, pp 283–289 | Cite as

Final results of a multicenter phase II clinical trial evaluating the activity of single-agent lapatinib in patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells. A proof-of-concept study

  • Marta Pestrin
  • Silvia Bessi
  • Fabio Puglisi
  • Alessandro M. Minisini
  • Giovanna Masci
  • Nicola Battelli
  • Alberto Ravaioli
  • Lorenzo Gianni
  • Roberta Di Marsico
  • Carlo Tondini
  • Stefania Gori
  • Charles R. Coombes
  • Justin Stebbing
  • Laura Biganzoli
  • Marc Buyse
  • Angelo Di Leo
Clinical trial

Abstract

This multicenter phase II trial was designed to evaluate the activity of lapatinib in metastatic breast cancer patients with HER2-negative primary tumors and HER2-positive circulating tumor cells (CTCs). In this study MBC patients with HER2-negative primary tumors and HER2-positive CTCs previously treated with at least a first-line therapy for metastatic disease received lapatinib 1500 mg/day. The CellSearch System® was used for CTCs isolation and bio-characterization. HER2 status was assessed on CTCs by immunofluorescence. A case was defined as CTCs positive if ≥2 CTC/7.5 ml of blood were isolated and HER2-positive if ≥50 % of CTCs were HER2-positive. 139 HER2-negative patients were screened, 96 patients were positive for CTCs (mean number of CTCs: 85; median number of CTCs: 19; range 2–1637). Seven of the 96 patients (7 %) had ≥50 % HER2-positive CTCs and were eligible for treatment with lapatinib. No objective tumor responses occurred in this population. In one patient, disease stabilization lasting 254 days (8.5 months) was observed. From the findings of this study, we concluded that a subset of patients with a HER2-negative primary tumor presents HER2-positive CTCs during disease progression, although the HER2 shift rate seems to be lower than previously reported. Despite the lack of objective response, the durable disease stabilization observed in one patient cannot rule out the hypothesis that lapatinib may have some activity in this patient population. However, considering that only 1/139 screened patients may potentially have derived benefit from this approach, future trials designed according to the presented strategy cannot be recommended.

Keywords

Circulating tumor cells HER2 Metastatic breast cancer Lapatinib 

Notes

Conflict of interest

Angelo Di Leo (Author # 16) and Fabio Puglisi (Author # 3) declare a consultant/advisory role with GlaxoSmithKline® and Roche®. Lorenzo Gianni (Author # 8) declares a consultant/advisory role with GlaxoSmithKline®. Other Authors have no conflicts of interest to disclose.

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Marta Pestrin
    • 1
  • Silvia Bessi
    • 2
  • Fabio Puglisi
    • 3
  • Alessandro M. Minisini
    • 3
  • Giovanna Masci
    • 4
  • Nicola Battelli
    • 5
  • Alberto Ravaioli
    • 6
  • Lorenzo Gianni
    • 6
  • Roberta Di Marsico
    • 7
  • Carlo Tondini
    • 8
  • Stefania Gori
    • 9
  • Charles R. Coombes
    • 10
  • Justin Stebbing
    • 10
  • Laura Biganzoli
    • 1
  • Marc Buyse
    • 11
  • Angelo Di Leo
    • 1
    • 12
    • 12
  1. 1.Medical Oncology UnitHospital of PratoPratoItaly
  2. 2.Translational Research UnitHospital of PratoPratoItaly
  3. 3.Department of Clinical OncologyUniversity Hospital of UdineUdineItaly
  4. 4.Department of Clinical OncologyHumanitas Cancer CenterRozzanoItaly
  5. 5.Medical Oncology UnitUniversity Hospital of AnconaAnconaItaly
  6. 6.Medical Oncology UnitOspedale degli InfermiRiminiItaly
  7. 7.Department of Medical OncologyOspedale CivileLivornoItaly
  8. 8.Medical Oncology UnitAzienda Ospedaliera Ospedali RiunitiBergamoItaly
  9. 9.Medical Oncology UnitSanta Maria della Misericordia HospitalPerugiaItaly
  10. 10.Department of OncologyImperial College Healthcare NHS TrustLondonUK
  11. 11.International Drug Development InstituteLouvain-la-NeuveBelgium
  12. 12.Ospedale di PratoPratoItaly

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