Background/Objectives: Breast cancer is the most common malignant neoplasm in women and the leading cause of cancer-related death. Approximately 50% of HER2-negative breast cancers exhibit low expression of this protein (HER2-low). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate targeting the HER2 receptor which has shown benefit in patients with HER2-low metastatic breast cancer in the DESTINY-Breast04 study. However, few data are available on its efficacy in real-world practice. Methods: We conducted a retrospective multicenter national study (eight centers) including patients with advanced HER2-low breast cancer (immunohistochemistry 1+ or 2+/ in situ hybridization negative) who started T-DXd treatment between January 2022 and March 2024. Patients had received at least one previous line of treatment. The primary endpoint was real-world progression-free survival (rwPFS) in patients with metastatic HER2-low breast cancer treated with T-DXd. The secondary endpoints were real-world overall survival (OS) and objective response rate (ORR). Results: The study included 35 patients (34 female and 1 male patient), with a median age of 54 years at the start of T-DXd. All patients had an ECOG-PS 0–1, and 26 patients (74%) had hormone receptor (HR)-positive disease. The median number of prior lines of treatment was 4 [1–7], and 23 patients (65.8%) had metastases in three or more sites. With a median follow-up of 7.8 months, rwPFS was 6 months (95% CI, 2.3–9.7), and OS was 15 months (95% CI, 4.7–25.3). In HR-positive patients, the median rwPFS was 6 months (95% CI, 1.2–10.7), compared to 4 months (95% CI, 2.1–5.9) in HR-negative patients. The overall ORR was 52.9%. Adverse events of grade 3 or higher were neutropenia (2.9%) and fatigue (2.9%). Conclusions: This study provides real-world data on T-DXd in the treatment of advanced HER2-low breast cancer. It is noteworthy that the population was heavily pre-treated and had a higher proportion of HR-negative patients, which may explain the lower efficacy compared to the DESTINY-Breast04 study.

Oxaliplatin is a platinum-based chemotherapy drug that is distinguished from others in its class by its neurotoxicity. This toxicity most commonly presents as a peripheral neuropathy with sensory symptoms, and less frequently as motor or autonomic disorders. Peroneal nerve palsy is a mononeuropathy presenting with foot drop and may result from multiple causes. Its occurrence in association with chemotherapy, particularly oxaliplatin, is rare. We report two cases of peroneal nerve palsy associated with oxaliplatin treatment. Case 1 involves a 73-year-old female with stage IV pancreatic adenocarcinoma who developed a left foot drop after four cycles of modified FOLFIRINOX (oxaliplatin 85 mg/m²). Neurological examination revealed distal weakness (3/5) without additional deficits. Electromyography confirmed axonal and demyelinating injury of the left common peroneal nerve (CPN). Other causes were ruled out. Following oxaliplatin discontinuation, the deficit completely resolved. Case 2 involves a 62-year-old male diagnosed with adenocarcinoma of the gastroesophageal junction who underwent neoadjuvant chemoradiotherapy with carboplatin (AUC 2) plus paclitaxel (50 mg/m²) and presented with metastatic disease five months later. After four cycles of FOLFOX (oxaliplatin 85 mg/m²), he developed a painless right foot drop with isolated motor deficit (0/5). Laboratory tests, brain CT, and spine MRI excluded alternative causes. Disease progression precluded further evaluation, and the patient died before the clinical course of the palsy could be assessed. These two cases highlight the potential of oxaliplatin-induced neurotoxicity to manifest as an isolated peroneal nerve palsy with foot drop. Given that only six cases of this condition have been described in the literature so far, further case reports are essential to better characterize risk factors, clinical course, and outcomes of this rare complication.