Age-related immune toxicity and treatment outcomes in triple-negative breast cancer treated with pembrolizumab.

e12710 Background: Tolerability and treatment completion of pembrolizumab added to neoadjuvant chemotherapy for triple-negative breast cancer (TNBC) varies across age groups. This study evaluated age-related patterns in immune-related adverse events (irAEs), pembrolizumab exposure, and clinical outcomes in TNBC treated with the KEYNOTE-522 regimen. Methods: We retrospectively analyzed consecutive TNBC patients treated with neoadjuvant ± adjuvant pembrolizumab from 2020–2025 at a multicenter single, academic, healthcare network. Patients were stratified by median age (53 years). Clinical, pathological, treatment, and toxicity data were abstracted. Outcomes included irAE incidence, treatment completion, pathological complete response (pCR), overall survival (OS) and progression free survival (PFS). Survival was assessed using Kaplan–Meier and multivariable Cox regression. Results: Among 125 patients, 36.8% developed immune-related adverse events (irAEs), including 15.2% with grade ≥3 toxicity. Younger patients had a higher incidence of irAEs than older patients (51% vs 31%; OR 2.19, 95% CI 1.05–4.43; p = 0.0326), developed toxicity earlier (mean 5.8 vs 7.2 cycles), and required systemic corticosteroids more frequently (OR 2.57, 95% CI 1.07–6.25; p = 0.0379). Younger patients received fewer neoadjuvant pembrolizumab doses (mean 6.17 vs 7.0) and were less likely to proceed to adjuvant pembrolizumab (OR 0.16, 95% CI 0.07–0.35; p < 0.0001). Despite reduced treatment exposure, pCR rates did not differ by age, and pCR was not associated with number of pembrolizumab doses received. OS did not differ by age alone (log-rank p = 0.4084). Achieving pCR was associated with markedly improved OS (HR 0.10, 95% CI 0.02–0.56; log-rank p = 0.0081) and PFS (HR 0.06, 95% CI 0.009–0.49; log-rank p = 0.0080), with this survival benefit significant in older patients (log-rank p = 0.0369) but not younger patients (log-rank p = 0.1537). Completion of adjuvant pembrolizumab improved OS (HR 0.17, 95% CI 0.04–0.75; log-rank p = 0.0193) and PFS (HR 0.17, 95% CI 0.03–0.89; log-rank p = 0.0360) overall, with benefit confined to older patients (log-rank p = 0.0258). On multivariable analysis, pCR was the strongest predictor of improved OS (HR 0.04, 95% CI 0.002–0.27; p < 0.01), while development of irAEs was associated with increased mortality risk (HR 7.95, 95% CI 1.27–70.78; p < 0.05). Conclusions: Age significantly influenced irAE risk, timing, and pembrolizumab feasibility. Younger patients maintained similar pCR and OS despite reduced treatment exposure, suggesting adequate immune activation may occur with shorter therapy. However, older patients derived greater survival benefit from completing the full regimen. Age-adapted immunotherapy strategies in early-stage TNBC should be evaluated.