Outcomes of elderly patients with early-stage triple-negative breast cancer treated with the KEYNOTE-522 regimen.

609 Background: The KEYNOTE-522 regimen (neoadjuvant pembrolizumab combined with a four-drug chemotherapy backbone, followed by adjuvant pembrolizumab) is a standard of care for stage II-III triple-negative breast cancer (TNBC). However, the median age of TNBC diagnosis is 40–50 years, and elderly patients (pts) are underrepresented in clinical trials. Methods: The effectiveness and safety of the KEYNOTE-522 regimen were evaluated in patients aged ≥65 years (y) in the Neo-Real/GBECAM-0123 trial, a real-world, multicenter study conducted across ten institutions since July 2020. Pathological complete response (pCR) was assessed as the primary endpoint. Patients < 65y served as the control group. Results: Of the 413 pts included in the study, 45 (10.9%) were aged ≥65y. Compared to younger patients, elderly pts exhibited a higher proportion of special histological types (15.6% vs 6.8%, P = 0.055), lower-grade tumors (grade 1–2: 35.5% vs 13.6%, P = 0.001), lower Ki-67 index ( < 50%: 46.7% vs 16.6%, P < 0.001), and fewer germline BRCA1/2 mutations (2.2% vs 13%, P = 0.039). The majority of patients in both groups had stage II disease (77.8% vs 69.3%, P = 0.574). Elderly pts were less likely to receive dose-dense anthracycline and cyclophosphamide (AC) (44.4% vs 55.4%, P = 0.027). Patients aged ≥ 65y had lower pCR rates compared to those < 65y (46.3% vs 64%; univariate logistic regression: OR 0.48, 95%CI 0.25–0.93, P = 0.030). However, this difference was not significant in multivariable analysis adjusted for histological type, tumor grade, Ki-67 index, BRCA status, and AC schedule (OR 1.80, 95% CI 0.74–4.37, P = 0.188). Elderly pts experienced significantly higher rates of safety concerns (Table 1). Conclusions: TNBC in elderly pts appears to have distinct biological characteristics, which may contribute to lower pCR rates with the KEYNOTE-522 regimen. Additionally, the higher incidence of safety issues in this population underscores the importance of personalized treatment strategies and careful patient selection. Further studies focused on elderly pts with TNBC are needed. Safety outcomes of elderly patients treated with KN522 regimen. ≥ 65y < 65y P Drug discontinuation due to AE AC discontinuation 33.3%17.8% 21.7%3.8% 0.1400.001 Dose reduction 27.2% 12.2% 0.010 Delay for neoadjuvant treatment conclusion 42.2% 22.3% 0.006 Hospitalization due to AE 33.3% 15.2% 0.011 Antibiotics use 44.4% 25.5% 0.019 Grade ≥ 3 AE Anemia Neutropenia Febrile neutropenia Fatigue 48.9%8.9%35.5%22.2%6.7% 34.2%2.4%19.6%10.3%1.4% 0.1370.0420.0200.0260.046