Successful treatment of gynecologic malignancy with trastuzumab deruxtecan in three patients with HER2 mutations

Abstract

Objectives: Trastuzumab deruxtecan is an antibody-drug conjugate that was recently FDA-approved as second-line therapy for advanced solid tumors expressing HER2 by immunohistochemistry at the 3+ level. Clinical trials have demonstrated trastuzumab deruxtecan's promise as a treatment for advanced gynecologic malignancies, which often have poor prognoses and limited treatment options. Here, we present three HER2 negative (IHC 0) or untested patients with HER2-mutated gynecologic cancers who derived significant benefit from trastuzumab deruxtecan.

Methods: Consent from patients to carry out this research was obtained, and their cases were reviewed via the electronic medical record. Relevant clinical, surgical, pathologic, and imaging data are described in this report.

Results: These patients with HER2-mutated disease benefited from trastuzumab deruxtecan despite being HER2 negative (IHC 0) or untested by immunohistochemistry and therefore not meeting current criteria for FDA-approved treatment with this drug. The first case describes a 65-year-old woman with recurrent high grade endometrial carcinoma who had a progression-free survival of over 12 months with trastuzumab deruxtecan. In the second case, a 76-year-old woman with recurrent low grade serous ovarian carcinoma received trastuzumab deruxtecan for over two years and continues the treatment at the time of this article's submission. The third case describes a 52-year-old woman with recurrent cervical mesonephric adenocarcinoma who had a 15-month long partial response to trastuzumab deruxtecan.

Conclusions: These cases illustrate the potential for trastuzumab deruxtecan to be useful among a broader range of patients than current guidelines include and suggest that comprehensive genomic testing is necessary to help identify patients whose disease may be susceptible to HER2-targeted therapies.

Fig. 1

CT imaging demonstrates response to treatment with T-DXd in Case 1. Focal metastatic lesion decreases in size from 33.5 mm x 25.4 mm (left) to 13.2 mm to 5.5 mm (right) with T-DXd treatment over the course of six months.

Fig. 2

CA-125 levels illustrate response to T-DXd in Case 1. CA-125 level fell from 177 to 23 after initiation of T-DXd and remained low while the patient received the drug.

Fig. 3

PET imaging demonstrates response to treatment with T-DXd in Case 2. Top row: Metastatic disease in the presacral area with decreasing avidity on PET imaging demonstrates patient’s response to treatment with T-DXd over time. Bottom row: Liver lesion with decreasing avidity and size after five and 15 months of T-DXd treatment also shows response to treatment.