Annals of Oncology Advance Access first published online on October 8, 2009
This version published online on November 2, 2009
Annals of Oncology, doi:10.1093/annonc/mdp373
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An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer
1 Department of Medical Oncology, Fondazione IRCCS Istituto Tumori, Milano, Italy
2 Medical Oncology Program, RS McLaughlin Durham Regional Cancer Centre, Oshawa, Ontario, Canada
3 Department of General Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan
4 Department of Oncology and Hematology, Universita degli Studi di Modena e Reggio Emilia, Modena, Italy
5 Department of Oncology, Hospital Olomouc, Olomouc, Czech Republic
6 Department of Medical Oncology, CHU Liège Hospital du Sart-Tilman, Liège, Belgium
7 Breast Cancer Department, The Hospital Associated With Military Medical Science, Beijing, China
8 Department of Medical Oncology, Royal Marsden NHS Foundation Trust & Institute of Cancer Research, London, UK
9 Breast Cancer Unit, Sheba Medical Center, Ramat Gan, Israel
10 Breast Link Medical Group, Inc., Long Beach, CA, USA
11 Breast and Endocrine Cancer Branch, National Cancer Center, Kyunggi-do, South Korea
12 Department of Hematology and Oncology, Marien Hospital Düsseldorf, Düsseldorf, Germany
13 Oncology Medicine Development Center, GlaxoSmithKline, Uxbridge, Middlesex, UK
14 Oncology Medicine Development Center, GlaxoSmithKline, Collegeville, PA, USA
15 Oncology, Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, Collegeville, PA, USA
16 Department of Molecular and Clinical Oncology, Universita degli Studi di Napoli Federico II, Napoli, Italy
* Correspondence to: Dr G. Capri, Fondazione IRCCS Istituto Tumori, Via Venezian 1, 20133 Milano, Italy. Tel: +39-02-2390-3048; Fax: +39-02-2390-2055; E-mail: giuseppe.capri{at}istitutotumori.mi.it
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.
capecitabine, EGFR, expanded access, HER2, lapatinib, metastatic breast cancer
The data in the second paragraph of the Discussion have been corrected.
Received for publication May 12, 2009. Accepted for publication May 29, 2009.