A phase II, randomized, multicenter study evaluating the combination of
lapatinib and vinorelbine in women with ErbB2 overexpressing metastatic
breast cancer
Lapatinib is approved in combination with capecitabine for treatment of
patients with human epidermal growth factor receptor 2 (HER2)-positive
metastatic breast cancer (MBC) who have progressed on prior trastuzumab
in the metastatic setting. Vinorelbine is an important chemotherapy
option for MBC. We evaluated efficacy and safety of lapatinib plus
vinorelbine, compared with lapatinib plus capecitabine, in women with
HER2-positive MBC. In this open-label, multicenter, phase II study,
eligible patients (N = 112) were randomized 2:1 to lapatinib plus
vinorelbine [(N = 75) 1,250 mg orally once daily (QD) continuously
plus 20 mg/m(2)/day intravenously] or lapatinib plus capecitabine [(N
= 37) 1,250 mg orally QD continuously plus 2,000 mg/m(2)/day orally, 2
doses]. The primary endpoint was progression-free survival (PFS). Other
endpoints included overall survival (OS) and safety. Patients
progressing within the study were given the option of crossover to the
other treatment arm; time to second progression was an exploratory
endpoint. Patient demographics, stratification, and prognostic factors
were well balanced between treatments. Median PFS in both arms was 6.2
months [95 % confidence interval (CI) 4.2, 8.8 (lapatinib plus
vinorelbine); 4.4, 8.3 (lapatinib plus capecitabine)]. Median OS on
lapatinib plus vinorelbine was 24.3 months (95 % CI 16.4, NE) and 19.4
months (95 % CI 16.4, 27.2) on lapatinib plus capecitabine. In total,
42 patients opted to cross over; median PFS was 3.2 months (95 % CI
1.7, 5.1) on lapatinib plus vinorelbine and 4.0 months (95 % CI 2.1,
5.8) on lapatinib plus capecitabine. Lapatinib plus vinorelbine offers
an effective treatment option for patients with HER2-overexpressing MBC,
having displayed comparable efficacy and tolerability rates to lapatinib
plus capecitabine