Antibody-Drug Conjugates as a Potential a Systemic Treatment Strategy for Brain Metastases in Cases of Solid Tumors

Abstract

Large molecular antibody-drug conjugates (ADCs) are able to easily access the site of metastasis in the brain due to the edematous structure of brain metastases, facilitating considerably high concentrations of the cytotoxic component of these ADCs in the intracellular and peritumoral environment. Therefore, these ADCs are expected to achieve deeper responses in brain metastases. In this context, the present study discusses the cases of two different patients. The first patient had lung adenocarcinoma with asymptomatic brain metastases, visceral metastases, and bone metastases, and was treated with Sacituzumab govitecan. The second patient had human epidermal growth factor receptor 2-positive breast cancer with lung and brain metastases and received treatment with Trastuzumab deruxtecan. The use of ADC achieved a complete response in brain metastases in both cases, as revealed by the results of cranial magnetic resonance imaging. Accordingly, it is suggested that efficacy evaluations regarding brain metastases should be investigated as a separate secondary endpoint in studies conducted on the use of ADC and that brain metastases should be included as a special research topic in antibody drug design and development.

Keywords

• immunoconjugates
• brain neoplasms
• brain edema