First line trastuzumab- or lapatinib-based therapy in her2-positive metastatic breast cancer patients after prior (NEO)adjuvant trastuzumab

Abstract

Background: Approximately 15‐20% of patients ( pts) with HER2‐positive early breast cancer relapse during or after (neo)adjuvant trastuzumab. The optimal first‐line treatment in this setting has been poorly investigated so far. We evaluated the clinical outcomes of HER2‐positive metastatic breast cancer (MBC) pts with prior exposure to (neo)adjuvant trastuzumab who underwent first‐line trastuzumab‐ or lapatinib‐based therapy. Materials and methods: This is an ancillary study within a retrospective cohort study conducted in 14 Italian centres of the GIM (Gruppo Italiano Mammella) group. Consecutive pts undergoing first‐line trastuzumab or lapatinib‐based therapy after prior exposure to (neo)adjuvant trastuzumab were included. Analyses were performed according to the type of first‐line therapy for metastatic disease (trastuzumab or lapatinib). Dichotomous clinical outcomes were analyzed using logistic regression and time‐to‐event outcomes using Cox proportional hazards models controlling for relevant demographic, clinicopathologic and therapy characteristics. All data were analyzed using Stata 12.3 (StataCorp LP). Results: Out of 450 MBC pts included in the study, 416 (92%) received trastuzumab and 34 (7.5%) lapatinib. A total of 128 pts relapsed after prior (neo)adjuvant trastuzumab and were included in the present analysis: 101 (24.3%) received first‐line trastuzumab and 27 (79.4%) lapatinib. As compared to the trastuzumab cohort, more pts in the lapatinib group had a trastuzumab‐free interval < 1 month (37% vs 14%) and brain metastasis as first site of relapse (38.2% vs 9.4%). In pts receiving first‐line trastuzumab or lapatinib, the following outcomes were observed, respectively: overall response rate (ORR) 61.3% vs 45.5% (p = 0.184), clinical benefit rate (CBR) 72.5% vs 68.2% (p = 0.691), median progression‐free survival (PFS) 12 vs 11.4 months (p = 0.814) and median overall survival (OS) 48.2 vs 34.7 months (p = 0.722). In pts who had brain metastasis as first site of relapse receiving first‐line trastuzumab or lapatinib, PFS was 9.9 vs 12.2 months (p = 0.093) and OS 28.5 vs 33.7 months (p = 0.280), respectively. Conclusions: In HER2‐positive MBC pts relapsing after prior (neo)adjuvant trastuzumab and receiving first‐line trastuzumab or lapatinib, no significant differences in their clinical outcomes were observed. Although not significant, atrend favouring the use of lapatinib was observed in pts with brain metastases as first site of relapse.