An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer

Ann Oncol. 2010 Mar;21(3):474-480. doi: 10.1093/annonc/mdp373. Epub 2009 Oct 8.

Abstract

Background: The Lapatinib Expanded Access Program (LEAP) was designed to provide access to lapatinib plus capecitabine for HER2-positive metastatic breast cancer patients who previously received an anthracycline, a taxane, and a trastuzumab and had no other treatment options.

Patients and methods: LEAP opened globally and enrollment continued until lapatinib received regulatory approval in each participating country. Patients were assessed for progression-free survival (PFS) and overall survival (OS) and monitored for serious adverse events (SAEs).

Results: As of 30 September 2008, 4283 patients from 45 countries enrolled in LEAP. The median treatment duration was 24.7 weeks. The most common drug-related SAEs were diarrhea (9.7%), vomiting (4.3%), and nausea (2.4%) and were mainly grade 3 or higher. The incidences of special interest SAEs were decreased left ventricle ejection fraction (0.5%), interstitial lung disease/pneumonitis (0.2%), and serious hepatobiliary events (0.4%). This safety profile is consistent with the overall lapatinib program. The median PFS and OS were 21.1 [95% confidence interval (CI) = 20.1-22.3] and 39.6 (95% CI = 37.7-40.7) weeks, respectively (n = 4006). Subgroup analysis showed longer PFS and OS in patients who had not received prior capecitabine.

Conclusions: These results demonstrate the safety and efficacy of lapatinib in a broader patient population compared with a clinical trial.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / secondary
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Capecitabine
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Follow-Up Studies
  • Humans
  • Lapatinib
  • Lymphatic Metastasis
  • Middle Aged
  • Quinazolines / administration & dosage
  • Receptor, ErbB-2 / metabolism*
  • Safety
  • Survival Rate
  • Treatment Outcome
  • Young Adult

Substances

  • Quinazolines
  • Lapatinib
  • Deoxycytidine
  • Capecitabine
  • Receptor, ErbB-2
  • Fluorouracil