Management of amivantamab-associated scalp toxicity: A multicenter retrospective cohort study.

e24207 Background: Scalp toxicities, namely erosive pustular dermatosis (EPD) and scalp folliculitis, are common and often challenging toxicities associated with amivantamab, a bispecific epidermal growth factor receptor / mesenchymal-epithelial transition (EGFR/MET) antibody for EGFR-mutant non-small cell lung cancer (NSCLC). While prophylactic strategies for preventing scalp toxicity have been identified in the COCOON study (oral tetracyclines, topical clindamycin, ceramide-based moisturization, and sun-protection), data on real-world management outcomes for this toxicity remain limited. Methods: We retrospectively identified patients with amivantamab-induced scalp toxicity at two tertiary academic centers from 5/2022-11/2025. Severity was graded with Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Clinical response was categorized as complete resolution, partial improvement, or no improvement. Results: Of 74 patients prescribed amivantamab, 15 patients had amivantamab-induced scalp toxicity. EPD was the predominant phenotype (12/15; 80%). Baseline severity was Grade 2 (9/15; 60%) or Grade 3 (5/15; 33.3%). In our cohort, 14/15 (93.3%) experienced clinical improvement with multimodal management, most commonly including high-potency topical corticosteroids (14/15; 93.3%), oral doxycycline (14/15; 93.3%), topical clindamycin (9/15; 60%), and oral retinoids (3/15; 20%). In three refractory cases, adding oral retinoids (isotretinoin or acitretin) to the initial regimen (with discontinuation of oral tetracycline), achieved partial improvement in two and complete clearance in one. Complete scalp toxicity clearance (Grade 0) was achieved in 8/15 (53.3%), particularly 2/5 (40%) patients with Grade 3 toxicity (3-grade improvement) and 6/9 (66.7%) with Grade 2 toxicity (2-grade improvement). Median time to complete resolution among patients with Grade 2 scalp toxicity was 77 days (range 75-96). Among patients achieving complete resolution (n = 8), 4 (50%) received a regimen that included high-potency topical corticosteroids, doxycycline, and topical clindamycin. While amivantamab dose modifications were required in 9/15 (60%) for cutaneous toxicities, all patients continued therapy. Conclusions: Scalp toxicities represent a frequent dose-limiting toxicity with amivantamab. Our study shows scalp toxicities with amivantamab are generally responsive to therapy comprising oral doxycycline, topical corticosteroids, and topical antibiotics. For refractory cases, escalation to oral retinoids demonstrated additional improvement, suggesting oral retinoids are a promising option for severe scalp toxicity. Study limitations include retrospective nature and small sample size. Our findings extend the prevention-focused COCOON data by providing outcomes-based evidence for strategies for managing scalp toxicities arising on amivantamab therapy.