Impact of pembrolizumab infusion timing on outcomes in early-stage triple-negative breast cancer: A real-world exploratory analysis (Neo-Real).

Abstract

610 Background: Neoadjuvant pembrolizumab combined with chemotherapy is the standard of care for early-stage triple-negative breast cancer (TNBC) based on KEYNOTE-522, improving pathologic complete response (pCR) and event-free survival (EFS). Emerging data suggest that immunotherapy timing may influence oncologic outcomes; however, evidence in early-stage TNBC and in combination regimens is limited. We conducted an exploratory real-world analysis to evaluate the association between infusion timing and clinical outcomes. Methods: Neo-Real/GBECAM-0123 is a multicenter real-world cohort including patients with early-stage TNBC treated with neoadjuvant pembrolizumab-based chemotherapy in Brazil and Argentina. In this analysis, patients treated between 2019 and 2024 with available infusion timing data were included. Infusion timing was classified as Early (≤20% of pembrolizumab infusions initiated at or after 14:00) or Late (>20% initiated at or after 14:00). The primary endpoint was pCR (ypT0/Tis ypN0). Secondary endpoints included EFS, defined according to KEYNOTE-522 criteria. Sensitivity analyses using timing definitions were performed. Results: Among 419 patients with available infusion timing data (Early: n=265; Late: n=154); 385 underwent surgery and were evaluable for pCR. Baseline clinicopathologic characteristics were largely balanced between groups, although stage III disease was numerically more frequent in the Early group (30.9% vs 23.6%, p=0.134). Treatment features, including use of dose-dense chemotherapy and number of neoadjuvant pembrolizumab cycles (median 8 in both groups), were similar. pCR rates did not differ according to infusion timing (Early: 62.5% vs Late: 64.1%; p=0.827). Late infusion timing was associated with improved EFS, with a 2-year EFS of 90.7% versus 82.7% (p=0.013). In multivariable Cox regression adjusting for age, clinical stage, pathologic response, tumor grade, histology, and number of neoadjuvant pembrolizumab cycles, Late infusion timing remained associated with improved EFS (HR 0.34; 95% CI 0.15–0.80; p=0.013). Sensitivity and subgroup analyses, including evaluation of the timing of the first pembrolizumab infusion using an earlier cut-off (11:00), as well as analyses by histology, clinical stage, and pathologic response, yielded consistent results. Conclusions: In this exploratory real-world analysis of patients with early-stage TNBC treated with neoadjuvant pembrolizumab-based chemotherapy, infusion timing was not associated with pCR. However, later infusion timing was associated with improved EFS. These findings contrast with observations reported in other tumor types and underscore the need for further studies to clarify the impact of immune checkpoint inhibitor infusion timing on clinical outcomes in TNBC.