Abstract PS4-12-29: Backbone optimization with dose-dense anthracyclines and prophylactic G-CSF improves pCR without added febrile neutropenia in pembrolizumab-treated TNBC: real-world evidence from Latin America

Abstract Background Pembrolizumab combined with neoadjuvant chemotherapy (NACT) is the standard of care for early triple-negative breast cancer (TNBC) based on KEYNOTE-522. Real-world data from Latin America are scarce, and the contribution of dose-dense anthracyclines (ACdd) to efficacy and safety remains underreported. Methods We conducted a retrospective, single-institution study including patients with stage II-III TNBC treated with pembrolizumab-NACT. The primary endpoint was pathologic complete response (pCR, ypT0/is ypN0). Secondary endpoints included Residual Cancer Burden (RCB), immune-related and hematologic adverse events, and febrile neutropenia (FN). Adverse events were graded per CTCAE v5.0. Results A total of 40 patients initiated pembrolizumab-NACT. ACdd was used in 32/40 (80%), with routine primary G-CSF prophylaxis. Among the 32 patients who underwent definitive surgery with evaluable pathology, pCR (RCB-0) was achieved in 26/32 (81.3%). Among non-pCR cases, 2 were RCB-1 (6.3%), 3 were RCB-2 (9.4%), and 1 was RCB-3 (3.1%). In the entire cohort (n=40), febrile neutropenia (FN) occurred in 5/40 (12.5%), while grade ≥3 neutropenia was observed in 25% (9 grade 3, 1 grade 4). The FN rate was comparable to KEYNOTE-522 (15.1%), despite the high prevalence of ACdd in this cohort. The most frequent immune-related adverse events were hypothyroidism (n=4) and adrenal insufficiency (n=4). Grade 3 toxicities included adrenal insufficiency (n=1), hepatitis (n=1), and rash (n=1). No grade 4-5 events were observed. Conclusions In this Latin American real-world cohort, pembrolizumab-NACT achieved a high pCR rate (81.3%) with an acceptable hematologic and immune-related safety profile. The widespread use of ACdd (80%) with prophylactic G-CSF may have contributed to enhanced efficacy without new safety concerns. These findings highlight the relevance of backbone optimization when integrating immunotherapy into TNBC treatment and provide valuable evidence from underrepresented regions. Disclosure of prior presentation: Portions of these data were previously presented at SCOM (Chile); this submission includes updated cohort size, ACdd utilization, and expanded efficacy and safety analyses. Citation Format: D. Bustos, M. Callahan, M. Vera, I. Saffie. Backbone optimization with dose-dense anthracyclines and prophylactic G-CSF improves pCR without added febrile neutropenia in pembrolizumab-treated TNBC: real-world evidence from Latin America [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 PS4-12-29.