Abstract Background: Antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) have transformed the treatment of metastatic breast cancer (MBC). However, ADC-related alopecia remains poorly characterized. The effectiveness of scalp cooling in this setting is also unclear. Here, we evaluated the incidence and patterns of alopecia in patients (pts) with MBC treated with T-Dx and SG explored the potential protective effect of cold cap use. Methods: We identified pts with MBC treated with ADCs between June 2014 to June 2024 at UCLA using institutional databases. Pts were included based on ICD-9/10 codes for MBC, documentation of ADC use, and keywords related to scalp cooling discussion/ use in provider notes. Data were extracted on alopecia prior to ADC initiation (baseline alopecia), cold cap use during treatment, and alopecia development during ADC therapy based on clinical notes, patient self-report, and photographic documentation. Pts were stratified by pre-treatment alopecia status and ADC regimen (T-DXd, SG, or both sequentially). Those with alopecia attributed to neo/adjuvant chemotherapy administered at least one year prior to diagnosis of MBC were considered to have no baseline alopecia. Descriptive analyses were conducted to explore associations. Results: A total of 103 pts with MBC received ADC; T-DXd (n = 39), SG (n = 38), or both sequentially (n = 26). Disease subtypes included HR+/HER2− (36.8%), HR+/HER2+ (13.6%), HR−/HER2+ (12.6%), and TNBC (36.8%). Median age at MBC diagnosis was 54 years (range 26-80), and median duration of ADC treatment was 6.3 months (range 0-52.5). In the T-DXd group, 10/39 (25.6%) pts had baseline alopecia. Of the 29 pts without baseline hair loss, 10 (34.5%) developed alopecia while others did not have clear documentation of hair loss. Overall, 7 (of 29) pts without baseline alopecia used cold caps (4 57.1% developed alopecia) and 22 did not (6 27.3% had hair loss). In the SG cohort, 12/38 (31.6%) pts had baseline alopecia. Among the other 26 pts, 12 (46.2%) developed hair loss. Cold caps were used in 3 pts (2 66.6% had alopecia); of the 23 who did not use cooling, 10 (43.5%) experienced hair loss. Among the 26 pts who received both ADCs sequentially, 11 (42.3%) had baseline alopecia. Of the remaining 15 pts, 6 (40%) developed hair loss (5 during SG, 1 during T-DXd). One patient used a cold cap and did not have alopecia; among the 14 pts who did not use cooling, 6 (42.9%) developed alopecia. Conclusions: Alopecia is a common treatment-related toxicity among pts with MBC treated with T-DXd and/or SG. In this study, scalp cooling during ADC therapy was infrequent and appeared to offer limited protection against ADC-related alopecia. These findings underscore the need to develop innovative strategies to reduce hair loss risk with currently approved ADCs, as well as need to develop novel ADCs that do not confer alopecia risk for pts with breast cancer. Citation Format: S. Alkassis, L. Zhang, E. Yang, M. Lipsyc-Sharf, K. McCann, N. McAndrew, A. Master, J. LaBarbera, M. Sedrak, N. Palaskas, K. Greene, M. Kuiper, J. Glaspy, D. Elashoff, R. Callahan, A. Bardia. Alopecia Associated with Antibody-Drug Conjugates and Impact of Cold Caps For Patients with 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 PS1-01-20.
Alkassis et al. (Tue,) studied this question.