Clinical and pathological factors predicting long-term disease control with lapatinib and capecitabine for patients with HER2 positive metastastic breast cancer: results from a multicenter retrospective study

Abstract

Background: The combination of the dual HER1/HER2 inhibitor lapatinib and capecitabine (LC) is a therapeutic option for patients ( pts) with HER2‐positive metastatic breast cancer (HER2 + MBC) after failure of trastuzumab‐based therapy. No clinical and/or pathological factors have been identified as predictive markers of efficacy for LC. We conducted this retrospective analysis to investigate factors associated with progression‐free survival (PFS) in pts with HER2 + MBC receiving LC. Patients and methods: Clinical and pathological data of 148 pts with HER2 + MBC treated from March 2007 to December 2013 with LC after failure of at least one prior trastuzumab‐based treatment (given either in adjuvant or metastatic setting) were collected from 13 Italian institutions. PFS and overall survival (OS) were estimated by Kaplan Meier method and compared with log‐rank test. A Cox multivariate analysis was performed to evaluate the association between clinical/pathological characteristics and risk of disease progression with LC. Results: At a median follow‐up of 41 months (IQR 23‐62), median PFS and OS were 7 and 21 months, respectively. Pts with PFS > 7 months had a significantly longer OS compared to those with PFS ≤ 7 months (36 vs 15 months; p < 0.001). In the multivariate analysis for PFS, HER2 luminal subtype (HR 0.53; C.I. 95% 0.29‐0.95, p< 0.03) and progressive disease to prior trastuzumab at the first tumor assessment (HR 0.30; C.I. 95% 0.10‐0.89, p< 0.03) were significantly associated with reduced risk of disease progression on LC, whereas visceral metastases before starting trastuzumab‐based therapy were associated with higher risk of progression on LC (HR 2.11; CI 95% 1.08‐4.12, p = 0.03). Stage at diagnosis, tumor grading, proliferation index, metastatic sites before starting LC, PFS after primary treatment for early breast cancer, PFS achieved with first‐line trastuzumab and treatment with trastuzumab beyond progression were not associated with PFS on LC. Conclusion: Pts treated with LC who achieved PFS > 7 months had significantly longer OS. HER2 luminal subtype and rapid disease progression with prior trastuzumab were associated with a longer PFS with LC. The latter finding suggests that the underlying mechanisms of primary resistance are different for trastuzumab and lapatinib. Additional biological studies are needed to investigate predictive markers of sensitivity and resistance to LC.