Prognostic Factors Influencing Progression-Free Survival in HER2-Positive Metastatic Breast Cancer Patients Who Were Treated With A Combination of Lapatinib and Capecitabine.

Original Article Eur J Breast Health 2023; 19(2): 128-133 DOI: 10.4274/ejbh.galenos.2023.2022-12-4 Prognostic Factors Influencing Progression-Free Survival in HER2-Positive Metastatic Breast Cancer Patients Who Were Treated With A Combination of Lapatinib and Capecitabine İzzet Doğan, Nail Paksoy, Naziye Ak, Sezai Vatansever, Pınar Saip, Adnan Aydıner Department of Medical Oncology, İstanbul University Institute of Oncology, İstanbul, Turkey ABSTRACT Objective: The aim was to assess the prognostic variables in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer patients receiving lapatinib plus capecitabine. Materials and Methods: Retrospective data on HER2-positive metastatic breast cancer patients who received lapatinib and capecitabine were analyzed. Survival outcome was obtained with Cox regression analysis and the Kaplan–Meier method. Results: The study included 102 patients. Forty-four (43.1%) patients had de novo metastatic disease. The most frequent metastatic sites were, in order, bone (61.8%), brain (57.8%), liver (35.3%), and lung (34.3%). All of the patients had previously received chemotherapy based on trastuzumab. With combined lapatinib and capecitabine, complete response was observed in 7.8%, partial response in 30.4%, and stable disease in 24.5%. Progressionfree survival was 8 (95% confidence interval, 5.1–10.8) months. In multivariable analysis, endocrine therapy (p = 0.02), de novo metastatic disease (p = 0.02), and age (p = 0.02) were prognostic factors for progression-free survival. However, the number of chemotherapy cycles with trastuzumab, palliative radiotherapy, history of breast surgery, and the number of metastatic sites were not significant in this respect. Conclusion: These results have demonstrated the effectiveness of lapatinib plus capecitabine in metastatic HER2-positive breast cancer patients. Furthermore, unfavorable prognostic factors for progression-free survival were shown to be hormone-negative tumor, de novo metastatic disease, and young age. Keywords: Breast cancer; metastasis; HER2/neu receptor; lapatinib; capecitabine Cite this article as: Doğan İ, Paksoy N, Ak N, Vatansever S, Saip P, Aydıner A. Prognostic Factors Influencing Progression-Free Survival in HER2-Positive Metastatic Breast Cancer Patients Who Were Treated With A Combination of Lapatinib and Capecitabine. Eur J Breast Health 2023; 19(2): 128-133 Key Points • The combination of lapatinib and capecitabine was effective in the treatment of human epidermal growth factor receptor 2 positive metastatic breast cancer. • Clinical and pathological factors affected the efficacy of the combination of lapatinib and capecitabine. • The combination of lapatinib and capecitabine was well tolerated in patients and side effects are generally easily managed. Introduction Breast cancer is the most common malignancy in women globally and the second most frequent cause of cancer-related death (1). Breast cancer is divided into subtypes with biologically different characteristics. Human epidermal growth factor receptor 2 (HER2) oncogene receptor can be detected in approximately 15–25% of breast cancer patients (2, 3). The HER2 receptor is a transmembrane protein with intracellular tyrosine kinase activity from the epidermal growth factor receptor family (4). It has functions in cell growth 128 Corresponding Author: İzzet Doğan; and differentiation. HER2 receptor positivity is detected by in situ hybridization and immunohistochemistry (IHC) methods. Many therapeutic agents target the HER2 receptor, such as trastuzumab, pertuzumab, lapatinib, trastuzumab emtansine, and trastuzumab deruxtecan, and have been using to treat many HER2-positive solid tumors, especially breast and gastric cancer. Trastuzumab is the first agent to used as a targeted therapy in the treatment of HER2-positive metastatic breast cancer patients. In patients whose disease progressed after trastuzumab-based therapy, Received: 12.12.2022 Accepted:03.01.2023 Available Online Date: 01.04.2023 ©Copyright 2023 by the Turkish Federation of Breast Diseases Societies / European Journal of Breast Health published by Galenos Publishing House. Doğan et al. Lapatinib and Capecitabine in Metastatic Breast Cancer tumor progression was delayed, and a trend towards an improvement in overall survival (OS) was achieved, although not statistically significant, with the combination of lapatinib plus capecitabine (LC) compared to only capecitabine (5, 6). In another study, the combination of LC was found to be superior in terms of progressionfree survival (PFS) compared to capecitabine alone in patients who had previously received multiple treatments (anthracycline, taxane, and trastuzumab) (7). There is a limited number of studies examining the factors affecting the time to progression with the combination of LC in HER2-positive metastatic breast cancer patients who have received previous treatment. The aim of this study was to examine the factors affecting the efficacy of the combination of LC. Materials and Methods Patient Inclusion and Data This study was designed as a cross-sectional, retrospective study. Ethics committee approval was obtained before the study, and our study was conducted according to good clinical practices guidelines. Patients who received treatment in a single oncology center between 2009 and 2020 were included in the study. The patients in the study were identified through the information processing system. All patients included in the study had metastatic breast cancer with HER2positive features and had previously received at least one series of cancer chemotherapy. Patients who received other treatments, such as pertuzumab and trastuzumab emtansine targeting the HER2 receptor, other than trastuzumab-based treatment, before LC treatment, and patients who did not have sufficient data were excluded from the study. Demographic and clinicopathological features of the study cohort were extracted from hospital files. All treatments (surgery, radiotherapy, systemic cancer treatments) given to the patients were also noted. Progesterone receptor and estrogen receptor (ER) positivity were determined by IHC. HER2 receptor positivity was diagnosed by IHC (score 3) or in situ hybridization methods. The patients used capecitabine 1000 mg/m2 twice a day (1–14 days every three weeks) and lapatinib 1250 mg/day. Treatment-related response assessments were performed radiologically (computed tomography or magnetic resonance imaging) every three months. LC combination-related response assessment was performed using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria. In addition, treatment-related adverse events were graded. Records of patient deaths were extracted from the death information system of the Ministry of Health. OS was calculated as the duration from the onset of LC to death from any cause. PFS was determined as the duration from the beginning of LC (...truncated)