Abstract

Abstract Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years Ahrong Ham1, Sewon Lee1, Jungmin Jo1, Soo Ji Hong2, Ji Eun Lee2, Haena Lee2, Sungchan Gwark2, Jeongshin An2, Hyun Goo Kim2, Jun Woo Lee2, Joohyun Woo2, Woosung Lim2, Byung-In Moon2, Sei Hyun Ahn2, Hye Ah Lee3, Kyoung Eun Lee1 1 Division of Hematology and Oncology, Department of Internal Medicine, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea 2 Department of Surgery, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea 3 Clinical Trial Center, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea Purpose: Over the last two decades, treatment landscapes for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) have shown remarkable growth with the development of drugs targeting HER2. The standard of care for HER2+ MBC has continued to change with the ongoing development of new anti-HER2 therapies. We aimed to provide a comprehensive analysis of HER2-targeted therapies, clinical characteristics, and treatment outcomes in real-world practice of HER2+ MBC patients over the past 20 years. Methods: Patients who received palliative chemotherapy with HER2+ MBC between 2000 and 2022 were analyzed. We derived cohorts of two groups with or without anti-HER2 containing therapies. Patients receiving multiple anti-HER2 therapies throughout the entire period of treatment were further analyzed according to treatment regimen. The progression-free survival for palliative first-line (PFS1), and overall survival (OS) were compared between groups. A multivariate Cox regression model was used to investigate predictors of survival outcome in HER2+ MBC. Results: A total of 185 patients were analyzed. Median age was 49 years (IQR, 42-56 years). 47 patients (25.4%) were initially diagnosed with de novo stage IV disease. Visceral metastases were found in 95 patients (51.4%). The median PFS1 was 3.9 months (without anti-HER2 therapy) versus 15.6 months (with anti-HER2 therapy) between two groups (P< 0.001). Likewise, the median OS was significantly improved in anti-HER2 therapy group (34.0 months vs. 70.5 months, P=0.010). As a result of confirming the difference in OS according to the type of anti-HER2 therapies during the entire period of treatment by correspondence analysis, significant improvement was found when two or three types of anti-HER2 were used (without anti-HER2 vs. 2 types of anti-HER2, P=0.009; without anti-HER2 vs. 3 types of anti-HER2, P=0.010). Interestingly, when analyzed by treatment regimen, trastuzumab (H) + pertuzumab (P), HP + TDM-1, and H + TDM-1 significantly improved OS over regimens without anti-HER2 (without anti-HER2 vs. HP, P=0.009; without anti-HER2 vs. HP + TDM-1, P=0.013; without anti-HER2 vs. H + TDM-1, P=0.028, respectively). HP + TDM-1 therapies significantly improved survival rate compared to H single containing regimen (P=0.029). Based on our multiple Cox regression model, visceral metastasis was a significant poor OS prognostic factor and two and three types of anti-HER2 therapies were associated better OS prognosis (visceral metastasis: HR=2.40, P=0.003; 2 types of ant-HER2: HR=0.29, P=0.001; 3 types of anti-HER2: HR=0.22, P=0.018, respectively). Conclusions: Anti-HER2 therapies significantly improved PFS1 and OS. Continuing treatment by changing anti-HER2 therapies may act as a better prognostic factor. Further prospective studies are required. Citation Format: Ahrong Ham, Sewon Lee, Jungmin Jo, Soo Ji Hong, Ji Eun Lee, Haena Lee, Sungchan Gwark, Jeongshin An, Hyun-Goo Kim, Jun Woo Lee, Joohyun Woo, Woosung Lim, Byung-In Moon, Sei Hyun Ahn, Hye Ah Lee, Kyoung Eun Lee. Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-17-02.

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