Abstract PS5-01-25: Long-term response Patterns in HER2-positive advanced breast cancer within the geicam/2014-03 (registem) study

Abstract Background: Breast cancer (BC) is a heterogeneous disease with distinct subtypes, each having different prognosis and treatment responses. RegistEM aims to understand the distribution of subtypes in advanced BC (ABC) and their clinical implications. Significant advances have led to better median overall survival (OS) in patients (pts) with HER2+ BC. Targeted anti-HER2 therapies have changed the management and prognosis of HER2+ ABC, although there is a lack of data from long-term responders (LTRs). Methods: ABC pts, either recurrent early BC (EBC) or de novo metastatic (dnMBC), diagnosed from Jan-16 to Dec-19, were enrolled in this ambispective non-interventional cohort study. Biological samples from primary tumors, metastatic lesions, and blood were collected. This subanalysis aims to better characterize LTRs among pts with HER2+ ABC receiving 1st-line (1L) or 2nd-line (2L) anti-HER2 targeted therapies. We defined LTR as pts who did not progress to 1L therapy for more than 35 months (mo.), or for more than 16 mo. in 2L therapy. BC subtype was assessed by immunohistochemistry (IHC) with or without in situ hybridization (ISH) in the most recent tumor sample before 1L therapy. In the current analysis, 1,900 pts from 38 GEICAM sites were included (database ongoing, cut-off date Mar 17, 2025). Results: 341/1,900 (18%) pts had HER2+ ABC, 133(39%) were considered as LTR and 197 (58%) as non-LTR (NLTR), 11 pts were excluded due to lack of information or not receiving systemic treatment for ABC. At ABC diagnosis, median age was 56 years (interquartile range 48-69), all pts were female (70% postmenopausal), 68 (51%) LTR and 77 (39%) NLTR had dnMBC (p=0.0881). Hormone receptors positive (HR+) were observed in 92 (69%) LTR and 122 (62%) NLTR. HER2 status was confirmed by IHC 3+ in 89 (67%) LTR and 140 (71%) NLTR, and ISH amplified in 55 (41%) LTR and 81 (41%) NLTR. A different pattern of metastatic spread was observed between LTR and NLTR (p0.01; χ2 test): visceral (58% vs. 76%), bone without visceral (27% vs. 16%), and only soft tissue (15% vs. 8%), respectively. Tumor burden with ≤2 locations was present in 57 (50%) LTR and 96 (49%) NLTR. Most frequent metastatic locations were lymph nodes (53%) and bone (51%), similar in both groups; more NLTR had liver (30% vs. 40%), lung (28% vs. 35%), pleura (2% vs. 11%), and brain (4% vs. 9%). Neo-/adjuvant therapy was given to 61 (95%) LTR and 112 (94%) NLTR with EBC, mainly chemotherapy (CT)/anti-HER2 (34% LTR vs. 38% NLTR), CT/endocrine therapy (ET)/anti-HER2 in 30% LTR, and CT in 22% NLTR, with 55 and 48 mo. as median time to ABC in LTR and NLTR, respectively. The most common 1L therapies in both groups were CT/biological therapy (BT) (33% LTR vs. 48% NLTR) and CT/ET/BT (50% LTR vs. 28% NLTR); BT was mainly anti-HER2 and antiangiogenics, and ET, aromatase inhibitors (AI). 2L-therapy was given to 57% LTR and 72% NLTR. Most common 2L therapies were BT (50% LTR and 59% NLTR), ET/BT (mainly AI plus anti-HER2) in LTR (29%), and CT/BT (anti-HER2 in 89%) in NLTR (20%). At database cut-off date and after a median follow-up of 46 mo, 1L median PFS (mPFS) was significantly longer in LTR patients: 50 mo. (95% confidence interval CI: 42-64) LTR compared to 12 mo. (95% CI: 10-13) in NLTR pts. No PFS event on 1L was seen in 52 (39%) LTR and 13 (7%) NLTR. 2L mPFS (95% CI) was 23 mo. (19-30) LTR vs. 5 (4-7) NLTR. Death was reported in 31/133 (23%) LTR and 149/197 (76%) NLTR, mainly because of PD (65% LTR vs. 77% NLTR). Median (95% CI) OS from ABC diagnosis was not reached in LTR and 34 mo. (31-38) NLTR. Conclusions: In our cohort, pts with HER2+ ABC classified as LTR more frequently had bone or soft tissue-only metastases compared to visceral disease. No significant differences were observed between LTR vs NLTR in terms of HR, HER2-IHC score (3+ vs. 2+), oligo- vs. non-oligometastatic presentation, or dnMBC vs recurrent EBC disease. Citation Format: I. Alvarez, Á. Guerrero-Zotano, J. Cruz-Jurado, S. Antolín, E. Galve, C. Rodríguez, M. Hernández, A. Tibau, C. Falo, J. Chacón, A. Miguel, Á. Rodríguez-Lescure, E. Adrover, M. Margelí-Vila, R. Andrés, S. Servitja, M. Merino, I. González, J. Alonso-Romero, R. Villanueva, M. Echarri, A. Antón-Torres, S. Varela, M. Ruíz-Borrego, J. Guerra, M. Corbellas, M. Escudero, S. Bezares, F. Rojo, S. López-Tarruella. Long-term response Patterns in HER2-positive advanced breast cancer within the geicam/2014-03 (registem) 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 PS5-01-25.