In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e14569-e14569
Abstract:
e14569 Background: The anti-EGFR therapy erlotinib was FDA approved for the treatment of patients with advanced pancreas cancer. Human epidermal growth factor receptor 2 (HER-2), a member of the ErbB family of growth factor receptor tyrosine kinases to which EGFR belongs, is found overexpressed in 20% of pancreatic cancers . Targeting EGFR and HER-2 with separate specific monoclonal antibodies showed synergistic inhibition of pancreatic cancer tumor progression in mice bearing xenograft of human pancreatic cancer cell lines. We performed an open-label single arm phase II study to evaluate the combination of lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER-2, and capecitabine in the second-line treatment of metastatic pancreatic cancer. Methods: Patients with metastatic, unresectable, gemcitabine-refractory pancreatic cancer with adequate performance status (ECOG 0-2) and normal hepatic and renal function were eligible. Patients received lapatinib 1,250 mg PO daily, and capecitabine 1,000 mg/m 2 PO twice daily on days 1-14 of each 21-day cycle. Restaging studies were performed every 2 cycles. The primary endpoint was median overall survival (OS). Secondary endpoints included response rate (RR) and progression free survival (PFS). Results: Between 9-2009 and 8-2011, 17 patients received treatment. Six of 17 patients (24%) had disease progression after 2 cycles, 2 of 17 patients (12%) progressed after 4 cycles and 4 of 17 patients (24%) had stable disease and received more than 6 cycles. The median number of treatment cycles was 3 (range 1-22 cycles). The median PFS was 9 weeks (95% CI 7.1-18.9). Median OS was 25 weeks (95% CI 11 -34). Grade 3 nausea, vomiting in 3 patients (17%), grade 3 diarrhea in 2 patients (12%), grade 3 limb edema in 1 patient (6%), and grade 3 fatigue in 1 patient (6%). Serum was collected at baseline, three weeks and time of disease progression for microRNA analysis to identify biomarkers correlated with clinical outcome. Conclusions: The combination of lapatinib and capecitabine is a tolerated regimen for patients with gemcitabine-refractory metastatic pancreatic cancer. Some patients were able to receive 6 or more cycles of therapy. Molecular analysis of patients’ biosamples is ongoing.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.e14569
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
