Abstract
3583 Background: Lapatinib is an orally active, reversible inhibitor of the tyrosine kinase activity of ErbB1 (EGFR) and ErbB2 (HER-2/neu). This multicenter, open-label, phase II study was designed to evaluate the safety and efficacy of single-agent lapatinib in patients with metastatic colorectal carcinoma, whose tumors progressed on first-line therapy with 5-fluorouracil in combination with irinotecan or oxaliplatin. Methods: Eighty-six (86) patients received 1250mg of oral lapatinib daily until disease progression or unacceptable toxicity. Safety and efficacy assessments were performed at 4-week and 8-week intervals respectively. Tumor response was determined by an independent review committee using RECIST guidelines. Results: The median age was 60 years (22–83) and median KPS was 90 (70–100). Patients were not selected based on ErbB expression; however, 54.2% and 44.1% of the patients had positive expression (+1, +2, +3) for ErbB1 and ErbB2, respectively. The most commonly encountered adverse events were: diarrhea (45% grade 1, 2, 5% grade 3), rash (33% grade 1, 2, 2% grade 3), fatigue (27% grade 1, 2, 2% grade 3), nausea (20% grade 1, 2, 1% grade 3), anorexia (16% grade 1, 2, 2% grade 3), and vomiting (14% grade 1, 2). In addition, 3 (3%) patients experienced a drug-related Grade 2 (≥20%) decrease in LVEF. All decreases in LVEF were asymptomatic and resolved within three weeks after discontinuation of lapatinib. One (1%) patient experienced a confirmed partial response; however, five patients experienced a minor response with cytoreduction of 20%, 22.4%, 22.8%, 26.8%, and 34% at week 8. Overall, five patients experienced clinical benefit with stable disease for ≥20 weeks. The median TTP and overall survival were 8 and 42.9 weeks respectively. Conclusions: Lapatinib was well tolerated, but demonstrated limited activity as second-line monotherapy in patients with recurrent metastatic colorectal cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
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