Background: Lapatinib, a tyrosine kinase inhibitor of human epidermal growth factor receptor 2 (HER2), has shown activity in combination with capecitabine in patients with HER2-positive advanced... Show moreBackground: Lapatinib, a tyrosine kinase inhibitor of human epidermal growth factor receptor 2 (HER2), has shown activity in combination with capecitabine in patients with HER2-positive advanced breast cancer progressive on standard treatment regimens. We present results on preapproval drug access for this combination in such patients occurring in the general oncology practice in the Netherlands. Methods: Patients with HER2-positive advanced breast cancer progressive on schedules containing anthracyclines, taxanes, and trastuzumab were eligible. Brain metastases were allowed if stable. Lapatinib 1250 mg/day was given continuously in combination with capecitabine moo mg/m(2) twice daily for two weeks in a three-week cycle. Efficacy was assessed by use of response evaluation criteria in solid tumours version I.O. Progression-free survival (PFS) and overall survival (OS) were calculated. Results: Eighty-three patients were enrolled from January 2007 until July 2008. The combination was generally well tolerated and the most common drug-related serious adverse events were nausea and/or vomiting (5%) and diarrhoea (2%). Seventy-eight patients were evaluable for response. Clinical benefit (response or stable disease for at least 12 weeks) was observed in 50 patients (64%) of whom 15 had a partial response and 35 stable disease. The median PFS and OS were 17 weeks (95% CI: 13 to 21) and 39 weeks (95% CI: 24 to 54), respectively. For OS, higher Eastern Cooperative Oncology Group (ECOG) status (p= 0.016), brain metastases at study entry (p=0.010) and higher number of metastatic sites (p=0.012) were significantly negative predictive factors. Conclusion: In a patient population with heavily pretreated HER2-positive advanced breast cancer lapatinib plus capecitabine was well tolerated and offered clinical benefit. Show less
