Abstract P6-06-45: Predictive significance of the mucocutaneous toxicities, but not dose intensity of capecitabine for the treatment of lapatinib plus capecitabine in patients with HER2 positive metastatic breast cancer
Authors: Araki K , Fukada I , Takahashi S , Ito Y 
Published: August 2014

Abstract
Background: There are no definitive predictive markers, except HER2 overexpression, for anti-HER2 therapeutic sensitivity of patients (Pts) with HER2-positive breast cancer. The aim of this study was to evaluate clinical predictive factors for lapatinib plus capecitabine (LAPCAP) in Pts with HER2 positive metastatic breast cancer (HER2MBC).
Methods: This retrospective observational study was used data from our single institutional medical record system from June 2009 to March 2013. Evaluation of female Pts with HER2MBC who were treated with LAPCAP (LAP at 1250 mg/day continuously plus CAP at 2000 mg/m2 on days 1 through 14 of a 21-day cycle) included baseline clinical characteristics, dose modifications of LAPCAP, clinical efficacy, and incidence of adverse events (AEs). Dose-intensity was compared with reference standard regimens. The Kaplan Meier method was used to estimate time to progression free survival (PFS).
Results: A total 76 Pts were included in this analysis. At a median follow-up of 20 months, median age was 56 years (range, 36 to 75) and 41 of 76 Pts had received prior (neo- or) adjuvant chemotherapy including 18 trastuzumab (Tmab) containing regimen. Visceral metastases (Mets) were identified in 49, bone Mets in 37, lymph nodes Mets in 36, brain Mets in 17, and chest wall Mets in 16. The median number of prior chemotherapy or hormonal therapy for MBC before LAPCAP was 2 (range, 0 to 13), and 66 of 76 Pts had previously received Tmab containing regimen with taxanes for 40 Pts, vinorelbine for 36, CAP for 29, and hormonal therapies for 15. In LAPCAP, the overall response rate was 21% including 2 CRs and 14 PRs, and the clinical-benefit rates which had more than 6-month SD was 60%. During initial 12 months observation, 93% of Pts had any AEs. The most common AEs were hand-foot syndrome (HFS) in 55 Pts. Those Pts who had HFS had better PFS than those who did not have (p = 0. 23×10−4). Since HFS was one of the well-known AEs associated with CAP, we sought whether CAP dose influenced PFS or not. However, we did not find any relationship between cumulative or relative dose intensity of CAP and PFS in Pts who treated with LAPCAP. Because several studies with EGFR-targeted agents showed a positive correlation between cutaneous toxicities and outcomes, we sought whether the incidence of any AEs other than HFS influenced PFS in 76 Pts. HFS, and diarrhea, as well as skin rash were statistically significant favorable factors (p = 0. 23×10−4, 0. 60×10−2, and 0. 28×10−1) in Log rank analysis. Furthermore, median PFS of Pts who had all 3 AEs (n = 21) were 377 days, while 84 days (n = 7) who had not (p = 0.58×10−8). We did not find any other clinical predictive factors except these 3 AEs. Furthermore, we compared 20 Pts with longer PFS who had more than 12-month to 26 Pts with shorter PFS that had less than 6-month. Longer PFS had more statistically significant incidence of diarrhea (p = 0. 49×10−2), HFS (p = 0. 49×10−2), and skin rash (p = 0.36×10−1) than shorter one.
Conclusions: In LAPCAP, dose of CAP did not influence PFS, but EGFR inhibitor related toxicities might be alternative predicative markers for LAPCAP in HER2MBC.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-45.