Exploring a Novel Approach to Spare Classic Chemotherapy in HER2-Low, ER-Positive Breast Cancer Based on Trastuzumab Deruxtecan Combined with Endocrine Therapy

• Published in: Oncology and therapy Vol. 12; no. 3; pp. 363 - 373
• Main Authors: Scafuri, Luca, Buonerba, Carlo, Di Lauro, Vincenzo, Tortora, Vincenzo, Cascella, Marco, Liguori, Luigi, Sciarra, Antonella, Sabbatino, Francesco, Diana, Anna, Marra, Antonio, Tarantino, Paolo, Trapani, Dario, Giuliano, Mario, Arpino, Grazia, Curigliano, Giuseppe, Di Lorenzo, Giuseppe
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01-09-2024; Adis, Springer Healthcare
• Subjects: Breast cancer; Editorial; Estrogen receptor-positive; HER2-low; Internal Medicine; Medicine; Medicine & Public Health; Neoadjuvant therapy; Trastuzumab deruxtecan; Neoadjuvant therapy; HER2-low; Breast cancer; Trastuzumab deruxtecan; Estrogen receptor-positive
• ISSN: 2366-1070; 2366-1089; 2366-1089
• DOI: 10.1007/s40487-024-00286-3

Background
Breast cancer presents diverse molecular subtypes affecting treatment strategies. Human epidermal growth factor receptor 2 (HER2)-low, hormone receptor-positive (HR+) breast cancer poses a challenge due to limited targeted therapies. Current neoadjuvant treatment primarily utilizes chemotherapy, with conflicting results regarding efficacy in patients with HER2-low breast cancer. Trastuzumab deruxtecan (T-DXd) shows promise in HER2-low metastatic disease, and preliminary evidence suggests synergy with endocrine therapy.
Objective
This editorial explores the hypothesis that neoadjuvant T-DXd with or without endocrine therapy offers efficacy in the clinical management of HR+/HER2-low breast cancer.
Methods
We propose a phase II study with two treatment arms: T-DXd + letrozole and T-DXd alone. The primary endpoint is the radiological complete response rate. Secondary endpoints include pathological complete response rate, safety, event-free survival, and overall survival. Exploratory analyses will compare the arms to identify potential for optimizing treatment efficacy and minimizing side effects.
Conclusions
This study design allows for initial assessment of T-DXd with or without endocrine therapy in the treatment of HER2-low breast cancer. The findings may pave the way for personalized treatment strategies and inform future research, potentially leading to a chemotherapy-sparing approach.