Background: Trastuzumab deruxtecan (T-DXd), a HER2-directed antibody-drug conjugate, has significantly advanced the management of HER2-expressing malignancies. However, interstitial lung disease (ILD) remains a clinically significant adverse effect. Despite increasing clinical use of T-DXd, real-world data on ILD incidence, characteristics, and outcomes—particularly in Middle Eastern populations remain limited. Methods: This retrospective study analyzed medical records of patients who received trastuzumab deruxtecan (T-DXd) at a tertiary care hospital. Data collected included demographics, tumor characteristics, prior treatments, and interstitial lung disease (ILD)-related outcomes. ILD events were identified and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Descriptive statistics were used to summarize baseline characteristics and ILD features. Univariate logistic regression was performed to assess potential risk factors associated with ILD development. Kaplan–Meier survival analysis was used to evaluate time-to-event outcomes, including time to ILD onset and resolution. Results: Among 65 patients with advanced stage IV cancer (90.8% with breast cancer), 16 (24.6%) developed ILD following T-DXd therapy. The median time to ILD onset was 125.5 days. The most common presenting symptoms were dyspnea and cough (50%). A history of ground-glass opacities was associated with increased odds of ILD (OR 2.7; p = 0.236), though not statistically significant. Patients with Grade ≥ 3 ILD had significantly lower oxygen saturation levels compared to those with milder grades (88.3% vs. 97.7%, p = 0.049). Median time to clinical resolution was 297 days (95% CI: 77.5–516). No significant associations were observed with smoking history, pulmonary metastases, or prior thoracic radiation. Conclusions: In this real-world cohort, ILD occurred in nearly one-quarter of patients receiving T-DXd, predominantly within the first six months of treatment. The findings highlight the importance of early respiratory symptom monitoring and pulse oximetry—particularly in patients with pre-existing pulmonary abnormalities. These results underscore the need for vigilant ILD surveillance strategies and further prospective studies to validate predictive risk factors and optimize management protocols.

Background: Hormone receptor-positive (HR+), Human Epidermal growth factor Receptor 2 (HER2-negative) metastatic breast cancer (MBC) represents a substantial proportion of breast cancer cases in Saudi Arabia. Despite the established efficacy of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, particularly Palbociclib, in randomized control trials, real-world data from local institutions in Saudi Arabia remain limited. Objectives: This study aimed to evaluate progression-free survival (PFS), overall survival (OS), and toxicity profile among HR+, HER2-negative MBC female patients treated with Palbociclib at King Fahad Medical City (KFMC). Methods: A retrospective study was conducted on female patients with HR+/HER2-negative MBC treated with oral palbociclib combined with endocrine therapy (ET) at KFMC between January 2021 and September 2024. Data were collected from electronic health records. Descriptive statistics were conducted using mean for continuous variables and frequency for categorical variables. Survival analyses were conducted using Cox regression, log-rank tests and Kaplan–Meier analysis. Results: A total of 169 female patients with HR+/HER2− MBC were included. In the first-line setting, the median PFS was 20.14 months (95% CI: 14.65–30.49), compared with 11.3 months (95% CI: 7.98–not estimable) in the second-line setting. For OS, the median OS values were 53.1 months (95% CI: 41.2–not estimable) in the first-line group and 23.7 months (95% CI: 18.5–not estimable) in the second-line group. Significant predictors of shorter PFS included age, Body Mass Index (BMI), type of ET, cancer type, line of therapy, family history of cancer, and history of VTE. Visceral metastasis (HR = 3.087; p = 0.0229) and ECOG performance status of 4 (HR = 13.86; p = 0.0156) were associated with significantly shorter OS. The most common hematological adverse events (AEs) were neutropenia (45.6%), followed by anemia (5.9%), leukopenia (5.3%), and back pain (5.3%). Most toxicities were managed with dose reduction, holding treatment, or supportive care. Conclusions: Palbociclib demonstrated favorable survival outcomes and a manageable safety profile, with neutropenia being the most common AE. This study provides region-specific real-world evidence supporting the use of Palbociclib in HR+/HER2− MBC. These findings align with global trial data and highlight the importance of individualized treatment in clinical practice.