The Lapatinib Expanded Access Programme

Global expanded access study of lapatinib and capecitabine

Reference:
Capri G, Chang J, Chen S, et al. An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer.
Ann Oncol. 2010;21:474–480.

Background:
The Lapatinib Expanded Access Programme (LEAP) was designed to provide access to Tyverb (lapatinib) plus capecitabine for HER2-positive metastatic breast cancer patients whose cancer had progressed after treatment with regimens that included an anthracycline, a taxane and trastuzumab who had no other treatment options. As a compassionate use study, the results from LEAP cannot be compared with EGF100151.

Purpose:
To provide access to treatment with Tyverb in combination with capecitabine prior to regulatory approval in participating countries and to further study the efficacy and safety of the regimen.

Methods:

  • Single-arm, open-label study conducted globally in countries where there was an intent to file for the registration of the combination of Tyverb and capecitabine. Patient recruitment in each country was continued until Tyverb regulatory approval was obtained.
  • Patients were eligible for inclusion if they had HER2-positive locally advanced or metastatic breast cancer that had progressed following treatment with an anthracycline, a taxane and trastuzumab.
  • Unlike the EGF100151 registration study, patients with central nervous system involvement, prior capecitabine therapy, a performance status of 0–2 and who were without measurable disease were eligible for enrolment.
  • A total of 4283 patients from 45 countries were enrolled in LEAP.

Results:

  • The median treatment duration of the combination therapy was 24.7 weeks (maximum 131.3 weeks).
  • Just under half of enrolled patients (49.3%, n=2112) discontinued therapy and entered the follow-up phase. The main reason for discontinuation was progressive disease (35.9%, n=1539).
  • The most common drug-related serious adverse events (grade 2 and above) were diarrhoea (9.7%), vomiting (4.3%) and nausea (2.4%).
  • Adverse events of special interest included left ventricular ejection fraction decreases, interstitial lung disease or pneumonitis, and serious hepatobiliary events, which occurred in 0.5%, 0.2% and 0.4% of patients, respectively.

Tyverb in combination with capecitabine: efficacy

Reference: 1. Capri G, Chang J, Chen S, et al. An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer. Ann Oncol. 2010;21:474–480.