Abstract PO3-12-12: Axial Neuropathy in Two Breast Cancer Patients receiving Fam-trastuzumab deruxtecan: A Case Report

Introduction. Fam-trastuzumab deruxtecan (T-DXd) is FDA approved for metastatic HER2-positive (HER2+) and HER2-low breast cancer (BC). Peripheral neuropathy is a side effect of T-DXd, with an incidence of 13%. Here we discuss two BC patients (pts) who presented with paresthesias of the trunk after receiving T-DXd. Case 1. A 51-year-old female with Stage IIIB cT4N2M0 left BC, estrogen receptor positive (ER+), progesterone receptor positive (PR+) and HER2+ was treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP), followed by mastectomy and axillary lymph node dissection, with downstaging to ypT3N2a disease. She was enrolled on a clinical trial comparing T-DXd with standard treatment for HER2+ BC with residual disease after neoadjuvant therapy, and was randomized to T-DXd arm. She also received adjuvant proton radiation therapy to the chest wall. One week after her third cycle of T-DXd she developed Grade 3 paresthesias on her trunk and proximal upper and lower extremities, stating she could not bend over or perform activities of daily living. She did not experience associated weakness or peripheral neuropathy. Symptoms improved to Grade 1 after initiation of gabapentin and delay of cycle 4 T-DXd by one week. She resumed T-DXd with dose reduction per protocol, and increase in gabapentin dose. She was seen by neurology who localized her sensory findings to T5-T9. She was recommended to undergo MRI spine, but was unable to do so, due to presence of tissue expander. Paresthesias have been controlled on dose reduced T-DXd and continued gabapentin. Case 2. A 56-year-old female with ER+, PR+, HER2-negative BC initially diagnosed in 1990, with local recurrence in 2005, treated with mastectomy, adjuvant chemotherapy, and adjuvant endocrine therapy, followed by development of metastatic disease to lung, liver, bone and skin in 2017. She received multiple lines of endocrine therapy, including aromatase inhibitors and fulvestrant, with cdk4/6 inhibitors and everolimus, but either progressed or was intolerant to all treatments. Skin biopsy in 2022 confirmed metastatic BC, which was ER+, PR+, and HER2 low (IHC2+, FISH nonamplified). She then received T-DXd, with clinical and radiographic response to treatment. After cycle 8 T-DXd, the patient was hospitalized for severe burning pain of her trunk and skin. Radiologic evaluation, including CT chest, abdomen, pelvis, and MRI spine, did not show an etiology of her pain, and showed stable metastatic disease to liver and bones, without evidence of cord or nerve root compression. Symptoms improved on pregabalin. She received an additional cycle of T-DXd with dose reduction, but ultimately declined further treatment. Symptoms resolved within 5 months of discontinuation of T-DXd. Discussion. These cases represent unusual events of axial neuropathy in two BC patients receiving T-DXd. Given the similarity of their symptoms, these findings may represent an unusual adverse effect of T-DXd. As the indications for T-DXd continue to expand, clinicians should be aware of this uncommon potential toxicity. Citation Format: Lauren Botero, Katharine McNeill, Della Makower. Axial Neuropathy in Two Breast Cancer Patients receiving Fam-trastuzumab deruxtecan: A Case Report [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-12-12.