Abstract 5229: Hair loss in cancer patients receiving small molecule inhibitors: Evidence from clinical trials

Abstract Alopecia remains one of the most common and distressing side effects of cancer therapy. While traditionally associated with cytotoxic chemotherapy, increasing evidence shows that small molecule inhibitors, targeting pathways such as FGFR, BRAF, and Src/ABL, can also induce clinically significant hair loss. However, incidence and severity patterns remain poorly characterized across small molecule inhibitor monotherapy. A scoping review of PubMed and Embase was conducted to identify clinical trials reporting alopecia in cancer patients treated with small molecule therapies. Eligible agents included kinase inhibitors (e.g., BRAF, KIT, FGFR, multikinase, Hedgehog pathway) and hormonal agents. Studies were excluded if they comprised preclinical studies, case reports, case series, reviews, or biologic therapies. Data on alopecia incidence, severity, and clinical presentation were extracted and synthesized qualitatively across small molecule drug classes. Eighteen clinical trials were included in this review, with alopecia incidence ranging from 9% to 63%. Hedgehog pathway inhibitors induced the highest overall rates, ranging from 20-30% with saridegib and glasdegib, and up to 63% with vismodegib. FGFR inhibitors (pemigatinib, infigratinib) and other kinase inhibitors (ripretinib, vemurafenib, sorafenib, AZD0424) demonstrated moderate rates (22-48%). Lower alopecia incidence was reported with aromatase inhibitors (anastrozole, lenostrozole) and the aurora B kinase inhibitor BI 811283, ranging from 9 to 21%. Across these monotherapies, alopecia was predominantly grade 1-2, with grade 3 alopecia or above occurring in less than 1% of patients. Although alopecia events were low-grade, their psychosocial impact remains significant. The higher incidences seen with Hedgehog inhibitors, compared with aromatase inhibitors, highlight how pathway-specific disruption of follicular signaling contributes to hair loss. Further research into the molecular mechanisms of these agents may help clinicians better anticipate and manage this side effect. Citation Format: Isabella Kamholtz, Simonetta I. Gaumond, Joaquin Jimenez. Hair loss in cancer patients receiving small molecule inhibitors: Evidence from clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5229.