Dent, Susan

ABSTRACT Introduction and Methods Cancer therapy–related cardiac dysfunction (CTRCD) is a well established and potentially life‐threatening complication of contemporary oncologic treatment. Although comprehensive cardio‐oncology guidelines have been developed, their integration into routine hematology and oncology practice remains inconsistent. This consensus statement, developed by a multidisciplinary panel of cardio‐oncology experts, aims to provide practical, case‐based guidance to help oncology providers recognize, assess, and manage CTRCD across a spectrum of malignancies and cardiovascular presentations. Clinical Scenarios and Discussion We present representative clinical scenarios that illustrate real‐world challenges in cardio‐oncology and apply evidence‐based recommendations from current guidelines, including those from the European Society of Cardiology (ESC) and the International Cardio‐Oncology Society (ICOS)—to support informed decision‐making. Key areas of focus include baseline cardiovascular risk stratification prior to initiating potentially cardiotoxic therapies, with an emphasis on biomarker and imaging surveillance strategies tailored to individual risk profiles. Also, this document outlines the application of guideline‐directed medical therapy (GDMT) for cancer patients with heart failure. Conclusion By offering a structured, user‐friendly framework, this document seeks to bridge the implementation gap between oncology and cardiology disciplines. Our goal is to equip oncology providers with accessible tools that facilitate early recognition, consistent surveillance, and timely referral, thereby preserving cancer treatment intensity while minimizing cardiovascular morbidity.

Abstract Background: Two years of adjuvant abemaciclib plus endocrine therapy is approved and guideline-recommended in patients (pts) with HR+, HER2-, node-positive, early breast cancer (EBC) at high risk of recurrence. In initial real-world studies, the high rate (>85%) of treatment (tx) persistence beyond 3 months suggests that adjuvant abemaciclib is well-tolerated in routine clinical practice.1,2 Dose reductions were associated with higher persistence in prior studies and clinical trial data have shown that efficacy of abemaciclib was maintained with dose reductions. This study describes 6-month tx persistence and dosing patterns in pts with HR+, HER2-, node-positive EBC initiating abemaciclib 150 mg twice daily (BID). Methods: Retrospective data were accessed from the US de-identified Flatiron Health Research Database. Adults with HR+, HER2-, node-positive, EBC, who initiated abemaciclib 150 mg BID from Jan 2022-Jun 2024 were eligible and further characterized by ≥1 vs no dose reduction. Data cut-off was Dec 2024. Persistence rate was the proportion of pts on abemaciclib >6 months, allowing for ≤60-day medication gap within this period. Time to dose modifications and reasons for discontinuation (DC) were summarized. Subgroup analyses were conducted in pts confirmed as meeting the monarchE high-risk criteria (N2, N3, or N1 plus Grade 3 and/or tumor >5 cm). All analyses were descriptive. Results: Of 1063 eligible pts, median age was 56 years (IQR 47, 65). Most had N1 (48%) or N2 (34%) disease. Median follow-up was 17.5 months (IQR 11, 25). Tx persistence at 6 months was 75%. DC was mostly due to adverse events (AEs; 19%) and <1% due to recurrence. Approximately 50% of pts had ≥1 dose reduction. Persistence was 85% in pts with ≥1 dose reduction and 64% in pts with no dose reductions. 70% of pts who DC’d by 6 months did not have a dose reduction. Median time from start of abemaciclib to first dose change and/or hold was 49 days (IQR 23, 111). During the first 30 days of tx and Days 31-90, DCs due to AEs were lower in pts with dose reductions vs pts with no dose reductions (Table). Persistence and use of dose reductions were similar in pts confirmed as meeting the monarchE high-risk criteria. Conclusion: In US clinical practice, a majority (75%) who initiated adjuvant abemaciclib continued abemaciclib beyond 6 months. Tx persistence was higher among pts with dose reductions relative to those with no dose reductions, and rates of early DCs due to AEs were low in pts with dose reductions. Given that dose reductions in monarchE were not associated with reduced efficacy, these additional real-world data support the use of early dose modifications to improve tolerability and tx persistence for adjuvant abemaciclib in pts with high risk of recurrence. Citation Format: H. Soliman, S. Dent, A. Liepa, V. Stefaniak, M. Huang, T. Sugihara, K. Moreira, K. Hudson, M. Goetz. Treatment Persistence and Dose Modifications in US Patients with HR+, HER2-, Node-Positive, Early Breast Cancer Treated with Adjuvant Abemaciclib [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 PS5-05-09.

Abstract Introduction: Hormone receptor positive (HR+), HER2- breast cancer (BC) is the most common subtype of BC. Despite advances in chemotherapy and endocrine therapy optimization, local and systemic recurrences frequently occur, especially for patients with node-positive disease. Recent data suggest a subset of patients with this tumor phenotype may benefit from the addition of anti-Programmed Death-1(aPD1) to neoadjuvant chemotherapy. However, T-cell infiltration (TCI), a biomarker of response to aPD1 and chemotherapy, is typically low in this BC subtype. Preclinical models show that combining preoperative radiation therapy (preop RT) with immune checkpoint inhibitors can enhance TCI and anti-tumor immunity. We conducted the first randomized trial to test whether no-, low- or high-dose RT combined with aPD1 increases TCI and improves responses in non-irradiated, metastatic lymph nodes in HR+/HER2- BC (NCT04443348). Materials & Methods: Eligible patients had ER and/or PR≥10%, HER2 negative invasive BC with clipped and biopsy-proven positive axillary node(s), cT1c-T4c, cN1-3, and at least one of the following criteria: grade 3 or grade 1-2 with cN2-N3, Ki67 >20%, or high genomic assay score. Between 2022-2024, 51 patients from 10 centers were randomized to no (0Gy; control arm), low (9Gy) or high (24Gy) doses of preop RT to the primary tumor with concurrent pembrolizumab followed by a 2-week tumor biopsy. Stratification factors were T1c vs. T2-4 and N1 vs. N2-3. Patients subsequently received pembrolizumab with 12 weeks of paclitaxel, followed by 4 cycles of adriamycin-cyclophosphamide (q2wk or q3wk) with pembrolizumab (200 mg q3 wks or 400 mg q6 wks). Surgery and adjuvant therapy followed standard-of-care. Dual co-primary endpoints were 2wk tumor TCI and nodal pathologic complete response (ypN0) at time of definitive surgery. TCI was assessed by multiplex immunofluorescence (pan-cytokeratin, CD3, CD8), using a rank-based Immunoscore (range 0-1), compared to baseline reference biopsies via two-tailed Mann-Whitney test. ypN0 was evaluated non-comparatively. Secondary endpoints included pCR and Residual Cancer Burden (RCB) 0/1. Results: Among 51 patients enrolled, 49 were evaluable for TCI and 48 for the ypN0 endpoint. Median age was 49.5 years (range 23-78). The cohort had a high-risk clinical profile: 92% had cT2-4, 50% N2-3, and 62% grade 3 tumors. Median ER and PR positivity were 90% (20-100) and 68% (1-98), respectively. Multifocal or multicentric tumors were present in 32%. TCI was assessed at 2 weeks post-treatment. The proportion of tumors with TCI in the upper quartile increased with RT dose escalation: 31% (0Gy), 40% (9Gy), and 53% (24Gy). Median TCI scores at 2 weeks were 0.60 (0Gy), 0.56 (9Gy), and 0.82 (24Gy), compared to a median baseline value of 0.50 from untreated reference samples. A statistically significant increase in TCI was observed only in the 24Gy cohort relative to the untreated group (p=0.027). 70.8% underwent mastectomy, with 39.6% receiving immediate reconstruction. 8% experienced G2/3 wound complications, balanced across arms. Median number of lymph nodes removed was 6.5 (1-42). The overall ypN0 rate was 29%, and 24%(0Gy), 29%(9Gy) and 33%(24Gy) per arm. pCR/RCB 0-1 rates were 18%/27% in the entire cohort and 6%/18%(0Gy), 29%/29%(9Gy), and 19%/33%(24Gy), respectively. Conclusion: The addition of 24Gy preop RT to aPD1 significantly increased tumor TCI in HR+/HER2- early-stage BC. Non-irradiated nodal response rates were promising despite over one-third of the study population with grade 1/2 tumors and high disease burden, laying the foundation for a future randomized trial comparing the efficacy of this novel approach against standard of care for node-positive HR+/HER2- BC. Citation Format: G. Gupta, A. Y. Ho, F. Gharibpoor, Y. Abdou, J. D. Anampa, R. C. Blitzblau, B. C. Calhoun, D. L. Casey, S. F. Dent, L. A. Carey, J. R. Bellon, L. E. Warren, J. Lu, T. J. Hieken, A. G. Taghian, A. Bardia, T. Traina, G. Plitas, K. Gallagher, K. Daugherty, A. Thompson, I. Krop, A. Wolff, E. Mittendorf, J. Fox, H. Garber, E. Hwang, A. J. Khan, J. P. Loene, R. Mutter, S. Patil, C. Santa-Maria, B. V. Vincent, J. L. Wright, L. Spring.Primary Results from the HR+/HER2- Cohort of TBCRC-053 (P-RAD): A Randomized Trial of No, Low, or High Dose Preoperative RADiation with Pembrolizumab and Chemotherapy in Node-Positive, HER2-Negative Breast Cancer [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 GS2-05.