Comparing safety & efficacy of AI/lapatanib/trastuzumab in HR+HER2 MBC

• Research type

  Research Study

• Full title

  A Phase III trial to compare the safety and efficacy of lapatinib plus trastuzumab plus an aromatase inhibitor (AI) versus trastuzumab plus an AI versus lapatinib plus an AI as first-line therapy in postmenopausal subjects with hormone receptor positive, HER2-positive metastatic breast cancer (MBC) who have received trastuzumab and endocrine therapy in the neoadjuvant and/or adjuvant setting.

• IRAS ID

  83724

• Contact name

  Stephen Johnston

• Sponsor organisation

  Novartis

• Eudract number

  2010-019577-16

• ISRCTN Number

  not known

• Research summary

  Research Summary

  This is a GSK sponsored study, in patients with hormone receptor positive (HR), HER2-positive (a protein present on the surface of some breast cancer cells) metastatic breast cancer (MBC). Metastatic means the cancer has spread beyond the breast to other parts of the body. Patients will be eligible to take part in this trial if: they are post-menopausal women; they received trastuzumab and either tamoxifen or an aromatase inhibitor before their cancer spread and they have not received any treatments since the cancer spread. If patients are eligible and wish to take part, they will be randomly allocated into one of three treatment groups:?½ Lapatanib Aromatase Inhibitor (AI)?½ Trastuzumab AI ?½ Lapatinib trastuzumab AI Patients will receive one of these treatments until the cancer grows (progresses). Patients may stop treatment if they experience unacceptable side effects, are unable to continue on treatment; or they request to leave the study. Patients will continue to have examinations after they stop taking study treatment. The main objective is to show if one of the treatments leads to a longer overall survival time than the others. One of the additional objectives is the measurement of progression free survival (time that the treatment prevents cancer growth).525 patients from the UK and across the world will take part in this study. Patients will be recruited from hospital clinics and need to attend regular visits to receive treatment and be examined by their doctors. Taking part may or may not benefit a patient??s health. Patients who take part may be seen more frequently by their doctors and nurses than those who do not. It is hoped that this study will contribute further information towards appropriate treatments for postmenopausal patients with HR, HER2-positive MBC.

  Summary of Results

  The final results of this study demonstrated similar efficacy results as observed in the primary PFS analysis demonstrating superior efficacy of the triple combination (lapatinib +trastuzumab
  +AI) by clinically meaningful reduction in the risk of progression or
  +death with lapatinib trastuzumab as compared to trastuzumab. The
  +results of the PFS were further supported by the
  key secondary endpoints, such as response rate, clinical benefit rate and median duration of response which also favored dual HER2 blockade.
  The safety profile of the three treatment groups was consistent with the known safety, and tolerability profile of lapatinib and trastuzumab in combination with AI. No new safety findings were identified.
  It can be concluded that treatment with anti-HER2 blockade with AI combination (lapatinib
  +trastuzumab +AI) represents an efficacious and safe treatment option
  +for subjects with HER2
  and HR positive metastatic breast cancer who had received prior trastuzumab and endocrine therapies.

• REC name

  London - Chelsea Research Ethics Committee

• REC reference

  11/LO/1619

• Date of REC Opinion

  13 Oct 2011

• REC opinion

  Favourable Opinion