Abstract PS5-10-24: Cardiac Monitoring in Patients Receiving HER2-Directed Therapy: A Meta-Analysis and Cost-Effectiveness Analysis

Abstract Background: HER2-targeted therapies improve outcomes in HER2-positive breast cancer but carry a risk of cardiotoxicity. Guidelines recommend routine LVEF monitoring every three months. However, the incidence of symptomatic heart failure appears low. We conducted a meta-analysis to quantify the risk of cardiotoxicity associated with HER2-directed agents and developed a cost-effectiveness model to evaluate alternative frequency of cardiac monitoring in patients with a standard cardiovascular risk profile. Methods: We performed a systematic literature search (Ovid MEDLINE, Embase, Cochrane) and included 55 studies (n=39,335) evaluating trastuzumab, pertuzumab, trastuzumab deruxtecan (T-DXd), and trastuzumab emtansine (T-DM1). A random-effects single-arm meta-analysis estimated the cumulative incidence of cardiotoxicity. Using these estimates and additional inputs estimated from the published literature, we constructed a decision-analytic model comparing four LVEF monitoring strategies during HER2-targeted therapy: (1) baseline only, (2) baseline and month 12, (3) baseline, month 6, and month 12, and (4) baseline plus every 3 months. We modeled early-stage breast cancer patients over 12 months of therapy. We used the model to project expected per-person cardiotoxicity events (i.e., heart failure with reduced ejection fraction, HFrEF) events detected and undetected, monitoring (i.e., echocardiogram) costs (including patient time), and incremental cost-effectiveness ratios (ICERs). We varied all model input values through plausible ranges in one-way sensitivity analyses. Results: Among 39,335 patients, the pooled incidence of any cardiotoxicity was 8.0% (95% CI 6.0-10.4) with trastuzumab, 1.4% (95% CI 0.8-2.6) with T-DM1, and 2.0% (95% CI 1.4-2.9) with T-DXd. Symptomatic cardiotoxicity was uncommon, occurring in 1.6% of patients treated with trastuzumab, 0.4% of patients treated with T-DM1, and 0.3% of patients treated with T-DXd. Cardiotoxicity rates were slightly higher in metastatic settings. In our initial cost-effectiveness modeling, more frequent monitoring was associated with more HFrEF events detected but at higher monitoring costs (Table 1), with an ICER of $390,500/HFrEF event detected for the strategy of baseline plus every 3 months compared to the strategy of baseline and months 6 and 12. Conclusions: HER2-directed therapies are associated with low rates of symptomatic cardiotoxicity, particularly T-DM1 and T-DXd. Cost-effectiveness modeling demonstrated diminishing returns with more frequent LVEF monitoring. Future analyses will assess the cost-effectiveness of LVEF monitoring strategies in patients with early-stage or metastatic disease treated with trastuzumab, T-DM1, or T-DXd. Citation Format: I. Schlam, M. C. Saad Menezes, J. N. Upshaw, J. Rabinowitz, J. Schwartz, A. Julian, V. Mico, S. Papatheodorou, N. Kunst, A. Pandya, A. Barac, S. M. Tolaney. Cardiac Monitoring in Patients Receiving HER2-Directed Therapy: A Meta-Analysis and Cost-Effectiveness Analysis [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 PS5-10-24.