Head Oncologist Bon Animal Medical center Seoul, Seoul-t'ukpyolsi, Republic of Korea
Abstract:
Background: Metastatic mammary carcinomas in dogs are aggressive malignancies with poor survival and limited treatments. Lapatinib, a tyrosine kinase inhibitor targeting HER2, has shown promise in human oncology. Its efficacy in canine metastatic mammary carcinomas requires further study.
Objective: Evaluate Lapatinib’s efficacy and tolerability in dogs with metastatic mammary carcinomas, focusing on HER2 expression as a therapeutic biomarker. Animals: Ten client-owned dogs with histologically or cytologically confirmed metastatic mammary carcinomas (Grade 2: n=1, Grade 3: n=5, inflammatory mammary carcinoma [IMC]: n=4).
Methods: This multi-center, retrospective pilot study assessed dogs treated with Lapatinib (20–27.4 mg/kg daily). HER2 status was determined via immunohistochemistry (scored 0–3+). Tumor response (RECIST), clinical benefit (CB: complete response [CR], partial response [PR], or stable disease [SD]), tumor-specific survival (TSS), and adverse effects (VCOG-CTCAE v2.0) were evaluated.
Results: Overall median TSS was 76 days (range: 14–412). HER2-positive cases (n=3) had a median TSS of 227 days (range: 52–412), HER2-negative cases (n=3) 139 days (range: 100–189), and IMC cases (n=4) 33.5 days (range: 14–43). Non-IMC (HER2-positive, HER2-negative) cases (n=6) achieved 100% CB with median CB duration of 102 days (range: 51–412). HER2-positive cases had longer CB duration (median: 227 days, range: 51–412) vs. HER2-negative (93 days, range: 65–111). One HER2-positive dog (score 2+) with pulmonary metastasis maintained SD for 227 days, and another (score 3+) achieved CR for 412 days; both remained alive at study closure. IMC cases showed progressive disease. Adverse effects in 7 dogs were mild, mainly Grade 1–2 liver enzyme elevations. Conclusions and Clinical Importance: Lapatinib showed efficacy in HER2-positive metastatic mammary carcinomas, prolonging survival compared to HER2-negative and IMC cases, with good tolerability. HER2 expression supports its role as a biomarker, warranting further study.
Learning Objectives:
Upon completion, participant will be able to understand the clinical efficacy and tolerability of Lapatinib as a targeted therapy in high-grade metastatic mammary carcinomas, focusing on its impact on HER2-positive, negative, and inflammatory mammary carcinoma cases and associated adverse effects.
Upon completion, participant will be able to understand past and current approaches for metastatic canine mammary carcinomas and identify key prognostic factors (e.g., histologic grade, metastatic status) that influence overall survival.
Upon completion, participant will be able to understand the role of HER2 receptor studies in canine mammary carcinomas, including EGFR in inflammatory mammary carcinoma, and their implications for targeted therapy development.
