Clinical Response to Novel Combination of Trastuzumab Deruxtecan and Abiraterone in HER2-Expressing Metastatic Castration-Resistant Prostate Cancer

Authors

Rithika Rajendran, The Edward P. Evans Precision Oncology Center of Excellence, Washington DC VA Medical Center, Washington, DC.
Coen J. Lap, The Edward P. Evans Precision Oncology Center of Excellence, Washington DC VA Medical Center, Washington, DC.
Siddharth Madapoosi, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Angela Heiraty, The Edward P. Evans Precision Oncology Center of Excellence, Washington DC VA Medical Center, Washington, DC.
Fayez Estephan, The George Washington University School of Medicine, Washington, DC, USA.
Winnie Hahn, The Edward P. Evans Precision Oncology Center of Excellence, Washington DC VA Medical Center, Washington, DC.
Aarati Poudel, The Edward P. Evans Precision Oncology Center of Excellence, Washington DC VA Medical Center, Washington, DC.
Victor E. Nava, The Edward P. Evans Precision Oncology Center of Excellence, Washington DC VA Medical Center, Washington, DC.
Ramesh Subrahmanyam, The Edward P. Evans Precision Oncology Center of Excellence, Washington DC VA Medical Center, Washington, DC.
Maneesh Jain, The Edward P. Evans Precision Oncology Center of Excellence, Washington DC VA Medical Center, Washington, DC.

Document Type

Journal Article

Publication Date

7-10-2025

Journal

The oncologist

DOI

10.1093/oncolo/oyaf207

Keywords

ADC; Abiraterone; HER2; Immunohistochemistry; Liver metastases; Prostate Cancer; Trastuzumab Deruxtecan

Abstract

Human Epidermal Growth Factor Receptor 2 (HER2) is expressed in approximately 60-70% of patients with metastatic castration-resistant prostate cancer (mCRPC) and may contribute to androgen resistance. This case report describes a patient with HER2-expressing mCRPC who progressed on multiple lines of therapy and subsequently had a significant response to combination treatment with the HER2-targeting antibody-drug-conjugate (ADC) trastuzumab deruxtecan (T-DXd) and re-challenge of abiraterone, despite having progressed on this prior. Unlike other HER2-expressing malignancies, HER2 overexpression in prostate cancer (PCa) occurs in the absence of HER2 mutations and amplifications and, as such, is not detected by next-generation sequencing. Therefore, identifying patients with mCRPC who could benefit from T-DXd necessitates HER2 testing by immunohistochemistry (IHC), a practice not routinely performed. As a result, T-DXd remains underutilized in patients with mCRPC, despite a tumor-agnostic approval for patients with advanced HER2-expressing (IHC 3+) solid tumors. This case highlights the potential of combining T-DXd with androgen receptor pathway inhibitors to overcome treatment resistance and underscores the importance of routine HER2 IHC testing in patients with advanced PCa.

APA Citation

Rajendran, Rithika; Lap, Coen J.; Madapoosi, Siddharth; Heiraty, Angela; Estephan, Fayez; Hahn, Winnie; Poudel, Aarati; Nava, Victor E.; Subrahmanyam, Ramesh; and Jain, Maneesh, "Clinical Response to Novel Combination of Trastuzumab Deruxtecan and Abiraterone in HER2-Expressing Metastatic Castration-Resistant Prostate Cancer" (2025). GW Authored Works. Paper 7616.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7616

Department

Medicine