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


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.
Capri
G
G
Department of Medical Oncology, Fondazione IRCCS Istituto Tumori, Milano, Italy. Electronic address: giuseppe.capri@istitutotumori.mi.it.
Chang
J
J
Medical Oncology Program, RS McLaughlin Durham Regional Cancer Centre, Oshawa, Ontario, Canada.
Chen
S-C
SC
Department of General Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan.
Conte
P
P
Department of Oncology and Hematology, Universita degli Studi di Modena e Reggio Emilia, Modena, Italy.
Cwiertka
K
K
Department of Oncology, Hospital Olomouc, Olomouc, Czech Republic.
Jerusalem
G
G
Department of Medical Oncology, CHU Liège Hospital du Sart-Tilman, Liège, Belgium.
Jiang
Z
Z
Breast Cancer Department, The Hospital Associated With Military Medical Science, Beijing, China.
Johnston
S
S
Department of Medical Oncology, Royal Marsden NHS Foundation Trust & Institute of Cancer Research, London, UK.
Kaufman
B
B
Breast Cancer Unit, Sheba Medical Center, Ramat Gan, Israel.
Link
J
J
Breast Link Medical Group, Inc., Long Beach, CA, USA.
Ro
J
J
Breast and Endocrine Cancer Branch, National Cancer Center, Kyunggi-do, South Korea.
Schütte
J
J
Department of Hematology and Oncology, Marien Hospital Düsseldorf, Düsseldorf, Germany.
Oliva
C
C
Oncology Medicine Development Center, GlaxoSmithKline, Uxbridge, Middlesex, UK.
Parikh
R
R
Oncology Medicine Development Center, GlaxoSmithKline, Uxbridge, Middlesex, UK.
Preston
A
A
Oncology Medicine Development Center, GlaxoSmithKline, Collegeville, PA, USA.
Rosenlund
J
J
Oncology Medicine Development Center, GlaxoSmithKline, Collegeville, PA, USA.
Selzer
M
M
Oncology, Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, Collegeville, PA, USA.
Zembryki
D
D
Oncology Medicine Development Center, GlaxoSmithKline, Collegeville, PA, USA.
De Placido
S
S
Department of Molecular and Clinical Oncology, Universita degli Studi di Napoli Federico II, Napoli, Italy.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D000077341:Lapatinib; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012449:Safety; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases