Abstract PS2-02-17: The High Unmet Need of Patients with Early Relapse After the KEYNOTE-522 Regimen - Evidence from the Neo-Real/GBECAM-0123 Study

Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of tumor characterized by early disease recurrence, with most events occurring within the first two years after definitive treatment. With the adoption of the KEYNOTE-522 regimen—pembrolizumab (P) added to neoadjuvant chemotherapy (NAC)—we aimed to describe the patters and rates of early recurrence events in a real-world population treated with this regimen. Methods: The Neo-Real/GBECAM-0123 study is a real-world data analysis of patients with TNBC treated with P+NAC at sites in Brazil and Argentina since July 2020. The current analysis evaluated recurrence patterns following P+NAC. Early recurrence was defined as recurrence occurring during or within six months after completion of neoadjuvant/adjuvant therapy. Disease progression during NAC that precluded surgery was also classified as early recurrence. Recurrence occurring more than six months after therapy completion was considered late recurrence. Event-free survival (EFS) was calculated from diagnosis to either progression preventing surgery, recurrence, or death from any cause. Overall survival (OS) was calculated from diagnosis to death from any cause. Results: A total of 726 patients were included. The median age was 44 years (range 21-91). Most patients had stage II disease (70.5%), grade 3 tumors (68.9%), and Ki-67 index ≥50% (71.1%); 105 patients (14.5%) had a known pathogenic BRCA1/2 variant. After a median follow-up of 22 months, 74 patients (10.2%) experienced disease recurrence, and 8 patients (1.1%) died without recurrence. The 2-year EFS was 86.9%. Among those with recurrence, 50 (67.6%) were classified as early (including 4 patients with disease progression during P+NAC, which precluded surgery) and 24 (32.4%) as late recurrences. Early recurrence occurred in 2.1% of patients with pCR and in 15.2% of those with residual disease (P < 0.001). From another perspective, among patients with early recurrence after surgery (n = 46), 80.4% (n = 37) had residual disease at surgery, while 19.6% (n = 9) had achieved pCR. Most patients with early recurrence received adjuvant therapy. In patients with pCR, 8 out of 9 (88.9%) received adjuvant P. Among patients with residual disease, 32 out of 37 (86.5%) received adjuvant treatment, including P plus capecitabine in 19 (51.3%), P alone in 6 (16.2%), capecitabine alone in 6 (16.2%), P plus Olaparib in 1 (2.7%). 5 patients (13.5%) received no adjuvant therapy, mainly due to early relapse. Among patients with pCR, the main recurrence sites were the central nervous system (CNS) (33.3%), lymph nodes (22.2%), pleura (22.2%), and locoregional (14.3%). For those with residual disease, the main sites were locoregional (33.3%), lymph nodes (24.3%), CNS (21.6%), bones (21.6%), lung (13.5%), and liver (13.5%). Post-recurrence deaths occurred in 18 patients with early relapse and 7 with late relapse. The 2-year OS rate in the overall cohort was 95.6%. Among patients with recurrence, the 2-year OS rate was 62.3% for those with early relapse and 91.0% for those with late relapse. Discussion: The majority of recurrences after the KEYNOTE-522 regimen occurred early. These patients are resistant to four chemotherapeutic agents and an immune checkpoint inhibitor (ICI) and face markedly poor survival outcomes. Our findings underscore a critical unmet need for effective therapeutic options in this population, which is often excluded from clinical trials investigating first-line regimens, including studies of antibody-drug conjugates combined with ICIs. Citation Format: R. Colombo Bonadio, L. Lapuchesky, M. C. Tavares, N. C. Nunes, L. Testa, I. Salas, M. Winocur, F. C. Balint, I. M. de Sousa, M. O. Andrade, M. C. Gouveia, F. Madasi, J. Bines, R. P. Ferreira, D. D. Rosa, C. L. Santos, M. R. Monteiro, Z. S. de Souza, D. Assad-Suzuki, C. dos Anjos, D. M. Gagliato, A. U. Gomes, B. M. Zucchetti, A. Ferrari, M. L. de Brito, M. F. Monteiro, P. A. Signorini, N. J. Gomes, G. G. Abuin, S. Sanches, M. Tavares, P. M. Hoff, M. Estevez-Diz, R. Barroso-Sousa. The High Unmet Need of Patients with Early Relapse After the KEYNOTE-522 Regimen - Evidence from the Neo-Real/GBECAM-0123 Study [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 PS2-02-17.