Abstract PS1-01-10: Chronic Immune-Related Adverse Events after neoadjuvant pembrolizumab in early-stage triple-negative breast cancer: A Real-World cohort analysis

Abstract Background: In early-stage triple-negative breast cancer (TNBC), the addition of immune checkpoint inhibitors (ICIs) such as pembrolizumab to (neo)adjuvant chemotherapy has significantly improved clinical outcomes, as demonstrated in the KEYNOTE-522 trial. This approach is now the standard of care in this population. However, the increasing use of ICIs in real-world settings raises concerns about chronic immune-related adverse events (irAEs), defined as toxicities persisting more than 12 weeks after treatment discontinuation. While chronic irAEs are well documented in melanoma and lung cancer, data remain scarce in early-stage TNBC, particularly in the curative setting. Methods: We conducted a retrospective, bicentric study (Institut Curie Paris and Saint-Cloud, France) involving patients with early-stage TNBC treated with pembrolizumab according to the KEYNOTE-522 regimen. All patients received at least one dose of neoadjuvant pembrolizumab. Chronic irAEs were assessed using CTCAE v5.0 criteria and defined as immune-related toxicities persisting beyond 12 weeks after pembrolizumab discontinuation, regardless of grade, starting from grade ≥2 (i.e., requiring medical intervention or impacting daily life). The primary endpoints were the incidence, type, duration, and management of chronic irAEs. Results: A total of 203 patients with stage II/III early TNBC were consecutively included between January 2021 and November 2023. The median age was 49 years (range: 22-74). Germline BRCA1 or BRCA2 mutations were identified in 14.8% of patients (n = 30), and 92.1% (n = 187) had invasive carcinoma of no special type. Postoperatively, 59% (n = 120) received at least one cycle of adjuvant pembrolizumab, while 41% (n = 83) did not, primarily due to limiting toxicities or the presence of residual disease. On average, patients received a total of 10 cycles of pembrolizumab (range: 1-17). The pathological complete response (pCR) rate was 70%. Chronic irAEs were reported in 36.5% of patients (n = 74). Endocrine toxicity was the most frequent, accounting for 79% (n = 58) of patients. Among these, hypothyroidism was observed in 62% (n = 36) and corticotropic insufficiency in 45% (n = 26); four patients experienced both. All endocrine events required long-term hormone replacement therapy, with no cases of functional recovery observed. Cardiac toxicity (myocarditis) was reported in 4.9% of patients (n = 10) and was managed with corticosteroids and standard cardioprotective therapies; no patient required second-line immunosuppression. Other chronic irAEs included gastrointestinal events in 2.0% (n = 4; 2 pancreatitis, 1 colitis, 1 gastritis), renal toxicity in 1.5% (n = 3; all interstitial nephritis), rheumatologic and neurologic events in 1.0% each (n = 2), pulmonary toxicity in 0.5% (n = 1; interstitial lung disease), and sicca syndrome in 1.0% (n = 2). Ten patients (4.9%) experienced multiple chronic irAEs. No deaths related to immune-mediated toxicity were observed. Conclusion: This real-world analysis reveals a high incidence of chronic irAEs among patients receiving curative-intent pembrolizumab for high-risk early-stage TNBC. These chronic irAEs can significantly impact quality of life, highlighting the urgent need for prospective studies and survivorship care planning for this growing population of breast cancer survivors. Funding: Collectif Triplettes Roses grant Citation Format: P. Matte, I. Hacini, P. H. Cottu, C. Helal, M. Mirabel, F. Coussy, F. Lerebours, E. Laas, E. Romano, L. Djerroudi, S. Hescot, P. Charles, B. Buecher, J. Pierga, L. Cabel, D. Loirat. Chronic Immune-Related Adverse Events after neoadjuvant pembrolizumab in early-stage triple-negative breast cancer: A Real-World cohort analysis abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-01-10.