Real-world distribution of antibody–drug conjugate (ADC)–associated adverse events (AEs) in breast cancer patients: An EPIC Cosmos database analysis.

Abstract

e13079 Background: AEs among ADC-treated breast cancer patients (BCPs) are associated with targeted antigens (TROP2, HER2) on normal tissue, payload direct and bystander effects, and ADCC-mediated cytotoxicity. Here we define real-world reports of incidence, distribution, and consequences of ADC-AEs and assess payload or antigen target roles in AE risk. Methods: ADC treated BCPs between 11/22 and 11/25 were identified in the EPIC-COSMOS dataset (n 2,304,438 in 310 health systems). ADC-treated BCPs were included who were prescribed ADCs within 3 months of BC diagnosis (dx) and had a BC dx documented as an encounter dx, admitting dx, billed final dx, billed admitting dx, billed charge-associated dx, or an active dx on the problem list in the query date range. AEs were assigned if they occurred within 6 months of ADC initiation. Results: Of 32,795 BCPs identified in the dataset, 28,040 had treatment-associated AEs (85.5%). HER2 was the dominant antigen target (75%) followed by TROP2 (23%). Most common payloads were emtasine (EM), deruxtecan (DER), and govitecan (GOV). ADCs, not typically used in BC were reported in 1% of cases. Across all ADCs, 76% of patients were aged 40y-75y. No difference in ADC use or frequency was noted as a function of either race or insurance coverage (White n 20,731[58.3%], AEs [58.8%]; Black or African American n 5,373 [15.1%], AEs 15.5%; Other 4,277 [12%], AEs 11.9%; Asian 1,424 [4%], AEs 3.9%). Of patients who received ADCs, AE frequency regardless of race was similar (range 76%-83.7%). Insurance type did not impact AE frequency (Commercial 40.5% of ADC patients; Medicare 37%; AE range [82.3%-85.8%]). Differences in the frequency and distribution of anemia, diarrhea, nausea, anorexia, neutropenia/febrile neutropenia (N/FN) were associated with payload (EM vs DER) not antibody target, but oral mucositis risk was more likely with TROP2- vs HER2-targeted ADC with similar payloads (Table 1). N/FN was more common in ADCs with DER (FN 14.8%) or GOV (29.8%) payloads vs EM (6.7%). Pneumonitis was rare ( < 1%). Of patients with AEs, hospitalizations varied by payload: EM 22%, GOV 57%, DER 47%, as did ICU admissions of ≥ 4 days (EM 14%, GOV 44%, DER 34%). Conclusions: RWD reported AEs are common among ADC-treated BC patients targeting HER2 or TROP2. AE distribution and outcome impact appear to be most impacted by ADC payload. Selected Adverse Event Rates Across Antibody–Drug Conjugates (N = 33,311). ADC Total Patients Anemia Diarrhea Fatigue Nausea Vomiting Alopecia Constipation Anorexia Oral Mucositis Abdominal Pain ado-trastuzumab emtansine 10,269 15.2% 7.3% 15.4% 13.1% 0.9% 1.0% 7.6% 2.7% 0.7% 5.0% datopotamab deruxtecan 259 16.2% 5.4% 9.7% 14.3% - - 10.0% 7.0% 8.5% 5.4% fam-trastuzumab deruxtecn 14,700 23.4% 15.0% 17.7% 23.8% 2.2% 1.6% 11.0% 7.7% 1.8% 7.4% sacituzumab govitecan 7,514 26.7% 18.1% 16.7% 21.0% 1.9% 1.2% 10.5% 8.4% 8.4% 8.7%