A phase II randomized trial of lapatinib with either vinorelbine or capecitabine as first- and second-line therapy for HER2 overexpressing metastatic breast cancer (MBC).

Abstract

516 Background: Lapatinib (L) is approved for the treatment of human epidermal growth factor receptor 2 (HER2) positive MBC in combination with capecitabine (C) following progression after trastuzumab, anthracyclines and taxanes. Vinorelbine (V) is an important chemotherapy option in MBC. This randomized, open-label, multicenter phase II study (NCT01013740) evaluated the efficacy and safety of L with either V or C in women with HER2+ MBC. The analysis of progression-free survival (PFS) and safety showed comparable rates of efficacy and tolerability between the 2 arms (Janni et al, SABCS 2012). Here we report the results of the overall survival (OS) and crossover analyses. Methods: Patients with MBC who had received ≤1 chemotherapy regimen in the metastatic setting were randomized 2:1 to either L 1250 mg orally once daily (QD) continuously + V 20 mg/m2 intravenously on days 1 and 8, every 3 weeks, or L 1250 mg orally QD continuously + C 2000 mg/m2/day orally in 2 doses, 12 hours apart on days 1-14 every 3 weeks. Patients were stratified by prior receipt of therapy for MBC and site of metastatic disease. The primary endpoint was PFS. Other endpoints included OS, overall response rate and safety. Patients progressing on one treatment arm were given the option of crossover to the other arm. All analyses were conducted with a descriptive intent only. The control arm of L+C was included in the study design to validate the patient population and lend support to the activity of L+V. Results: 112 patients were randomized in the study; 37 to the L+C arm and 75 to the L+V arm. The median OS in the L+C arm was 19.4 months [95% CI: 16.4-27.2] and 24.3 months [95% CI: 16.4-NE] in the L+V arm. At the time of analysis 42 patients had crossed over; 29 patients to L+C and 13 to L+V. Median PFS after crossover was 4 months [95% CI: 2.1-5.8] in the L+C arm and 3.2 months [95% CI: 1.7-5.1] in the L+V arm. Conclusions: L+V has shown consistent median OS with that reported in the pivotal study of L+C. The exploratory analysis of patients retreated with L after progression on L supports the biological rationale for maintaining HER2 suppression in HER2+ patients with progression on prior lines of anti-HER2 agents. Clinical trial information: NCT01013740.