Purpose: Patients with prostate cancer (PCa) treated with apalutamide frequently develop rash. We aim to characterize apalutamide-related dermatological adverse events (dAEs) and management. Materials and Methods: We assessed 303 patients with PCa treated with apalutamide. DAE frequency and time to onset were calculated and clinicopathological features and management described. Associations between dAE occurrence and clinical trial participation, as well as abiraterone/prednisone exposure were detected using logistic regression models.Results: Seventy-one (23.4%) patients had all-grade dAE occurring at a median of 77 (IQR: 30e135) days post-exposure. Twenty (6.6%) dAE-related therapy interruptions included: 8 (2.6%) with dose maintained on rechallenge, 7 (2.3%) with dose reduction and 5 (1.7%) with discontinuation. Common dAEs were maculopapular rashes (33.8%) and xerosis (32.4%). Seven (77.8%) of 9 histological analyses of skin biopsies supported a drug reaction. No significant differences in laboratory hematological, hepatic and renal function were detected between dAE and no dAE cohorts. Most treated grade

Spontaneous coronary artery dissection is a rare condition, usually presenting as an acute coronary syndrome, and is often seen in states associated with high systemic estrogen levels such as pregnancy or oral contraceptive use. While topical hormonal replacement therapy may result in increased estrogen levels similar to those documented with oral contraceptive use, there are no reported cases of spontaneous coronary dissection with topical hormonal replacement therapy. We describe a 53-year-old female who developed two spontaneous coronary dissections while on topical hormonal replacement therapy. The patient had no other risk factors for coronary dissection. After withdrawal from topical hormonal therapy, our patient has done well and has not had recurrent coronary artery dissections over a one-year follow-up period. The potential contributory role of topical hormonal therapy as a cause of spontaneous coronary dissection should be recognized.

Oral ruxolitinib has been successfully used for the treatment of acute and chronic graft-versus-host disease (cGvHD) and topical ruxolitinib has demonstrated efficacy in clinical trials for vitiligo, atopic dermatitis, and psoriasis. Background: There are no FDA-approved topical treatments for cutaneous cGvHD. Topical corticosteroids are the mainstay of skin-directed therapy for the inflammatory-phase cutaneous cGvHD but are associated with significant side effects such as skin thinning, bruising, striae, infections, and acne, and may incompletely treat cutaneous cGvHD, prompting use of systemic therapies. Methods. We conducted a prospective, randomized, double-blind, vehicle- and comparator-controlled, phase 2, proof-of-concept trial evaluating the efficacy and safety of topical ruxolitinib 1.5% cream in patients 12 years of age or older with cutaneous nonsclerotic (lichen-planus like, poikilodermatous) and superficially sclerotic (lichen sclerosus, morphea-like) cGvHD with ≥2% of body surface area (BSA) affected at a single, academic transplantation center in the United States. Patients were only eligible to enroll if systemic therapy, when applicable, was stable for ≥ 4 weeks and concurrent topical therapy (including phototherapy) was not used. Patients were randomly assigned (1:1) to receive topical ruxolitinib 1.5% cream left side of face/body or right side of face/body with placebo vehicle cream to contralateral side of face/body twice daily to for 28 days, followed by an optional open label extension to both sides of 28 days for interested patients. The primary end point was efficacy as measured by BSA of the GvHD rash on the side of face/body treated with topical ruxolitinib cream vs contralateral side treated with vehicle at Day 28. Secondary endpoints were Physician's Global Assessment of clinical condition (PGA) and Composite Assessment of Index Lesion Severity (CAILS) of the ruxolitinib-treated side vs vehicle-treated side at Day 14 and 28. Interim analyses were performed once 10 patients were evaluable of the planned 24 patients. Results. Between 6/28/19 and 5/14/21, a total of 13 patients (mean age 52.6 years [SD 20.0]; 7 [54%] female and 6 [46%] male) underwent randomization; 11 patients completed Day 14 assessments, 12 patients Day 28 assessments, and 10 patients Day 56 assessments. Patients had a history of acute leukemia (N=8 [62%]), non-Hodgkin lymphoma (N=3 [23%]), myeloproliferative neoplasm (N=1 [8%]), or aplastic anemia (N=1 [8%]). Median time from transplant to enrollment was 665 days (IQR 433-1355), and from cGvHD onset to enrollment 283 days (IQR 115-867). Chronic GvHD was NIH mild (8%), moderate (23%), or severe (62%), predominantly classic (85% vs. overlap 15%), with 46% having 4 or more involved organs. Most patients were enrolled for treatment of cutaneous nonsclerotic cGvHD (N=10, 77%) with lichen planus-like (N=8), papulosquamous (N=1), and maculopapular rash/erythema features (N=1). Three patients were enrolled for treatment of lichen sclerosus-like cGvHD. Patients were heavily pretreated with 4 (31%) having 3 or more prior lines of systemic therapy for cGvHD. Most patients had failed at least 2 topical therapies, with 77% previously failed topical steroids, 24% topical calcineurin inhibitors, and 24% phototherapy. There was a trend in reduced BSA of cGvHD on the treatment side compared to the vehicle side from Day 1 (13.4 on treatment/vehicle) to Day 14 (10.9 vs 13.8; p=0.06) and continuing to Day 28 (7.7 vs 11.0; p=0.15), respectively. PGA (Day 1: 5 treatment/vehicle) of treatment side was significantly improved starting at Day 14 (3.3 treatment vs 4.4 vehicle; p=0.024), with continued improvement at Day 28 (2.5 vs 4.0; p= 0.026). CAILS (Day 1: 15.6 treatment vs 15.5 vehicle; p=0.83) of treatment side was also significantly improved starting at Day 14 (9.0 vs 13.3; p=0.02). There were no serious adverse events (SAEs) reported. One patient had a grade 1 headache which was attributed possibly to therapy. Three patients had treatment-emergent AEs (all grade 1) that were unlikely (N=1) or unrelated (N=2) to study therapy. Conclusions. Topical ruxolitinib 1.5% cream was effective in treating cutaneous nonsclerotic and superficially sclerotic GvHD as determined by PGA and CAILS. These data suggest that ruxolitinib cream might be a safe and effective treatment option for patients with cutaneous nonsclerotic and superficially sclerotic chronic GvHD. Figure 1 Figure 1. Disclosures Markova: Alira Health Ventures: Consultancy; Incyte Corporation: Research Funding; Blueprint Medicines: Consultancy; UpToDate: Patents & Royalties: Royalties for chapter on dermatologic adverse events to targeted therapies ; Amryt Pharma: Research Funding. Perales: MorphoSys: Honoraria; Omeros: Honoraria; Cidara: Honoraria; Incyte: Honoraria, Other; Equilium: Honoraria; Medigene: Honoraria; Kite/Gilead: Honoraria, Other; Karyopharm: Honoraria; Sellas Life Sciences: Honoraria; Novartis: Honoraria, Other; Nektar Therapeutics: Honoraria, Other; Servier: Honoraria; Miltenyi Biotec: Honoraria, Other; NexImmune: Honoraria; Celgene: Honoraria; Merck: Honoraria; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria. Prockop: Memorial Sloan Kettering Cancer Center: Other: S Prockop receives support for the conduct of sponsored clinical trials through MSK from Atara Biotherapeutics, Jasper and AlloVir. , Patents & Royalties: S Prockop is a co-inventor on intellectual property (IP) licensed to Atara. S Prockop has waived rights to this IP to MSK and has no personal financial interests in Atara. MSK has financial interests in Atara and IP interests relevant to this abstract. ; MSK: Other: Inventor; Neovii: Consultancy; ADMA Biologics: Consultancy; Jasper: Other: support for the conduct of sponsored trials; AlloVir: Other: support for the conduct of sponsored trials; Atara Biotherapeutics: Other: support for the conduct of sponsored trials and Inventor. Ponce: Kadmon pharmaceuticals: Consultancy, Honoraria; Ceramedix: Consultancy, Honoraria; CareDx: Consultancy, Honoraria; Seres Therapeutics: Consultancy, Research Funding; Generon Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Research Funding.

12022 Background: Late alopecia is defined as incomplete hair regrowth > 6 months following cytotoxic chemotherapy or from initiation of endocrine therapy. It has been reported in up to 25-30% of cancer survivors and is associated with decreased quality of life and reduced dose intensity of cancer therapies. Minoxidil is an aminopyridine potassium channel opener, resulting in vasodilation and premature entry of resting hair follicles into the anagen (growth) phase and increase in hair follicle size. This study aims to assess clinical outcomes and adverse events of oral minoxidil for the treatment of cancer therapy-related late alopecia. Methods: We retrospectively assessed all women with late alopecia treated with oral minoxidil (1.25 mg daily) evaluated at an oncodermatology referral program between 1/2018-5/2021. Outcomes were assessed by standardized photography (4 views) and trichoscopy (HairMetrix, Canfield Scientific, Inc.). Trichoscopy recorded hair density (hair count/cm2) and hair thickness (shaft diameter) at uniform frontal and occipital target areas (12 and 36 cm midline from the glabella, respectively). Adverse events were recorded and graded using CTCAE v5.0. Descriptive statistics were used to summarize the patient demographics and clinical characteristics. Changes in trichoscopy measurements from baseline to follow-up were estimated using paired t-tests. Results: Two hundred and sixteen patients (mean age 57.8±13.7) were included for analysis. Thirty-one (14%) received chemotherapy alone, 65 (30%) endocrine monotherapy, and 120 (56%) chemotherapy followed by endocrine therapy. The majority of patients (n = 170, 79.1%) had a history of breast cancer. Standardized photography assessments (n = 119) after a median of 105 days (IQR = 70) on oral minoxidil revealed clinical improvement in 88 (74%). Trichoscopy assessments (n = 42) after a median of 91 days (IQR = 126) demonstrated increased frontal hair density (124.2 vs 153.2 hairs/cm2, p = 0.008) and occipital hair density (100.3 vs 123.5 hairs/cm2, p = 0.004). There was no statistically significant difference in average frontal or occipital hair thickness (69.3 vs 67.3 μm, p = 0.22, and 70.3 vs 69.9 μm, p = 0.84, respectively). No patients reported discontinuation of oral minoxidil due to adverse effects. Conclusions: Oral minoxidil may benefit both frontal and occipital late alopecia in cancer survivors treated with cytotoxic and/or endocrine therapy. This regimen was well tolerated by patients. Prospective, controlled studies are needed to confirm these observations.

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Background: Cutaneous Metastases (CM) are an infrequent presentation of advanced solid tumors and are usually associated with symptoms of pain, pruritus, and secondary infections, all of which negatively affect quality of life and result in additional morbidity. Systemic chemotherapy, advanced wound care, topical agents, cryo-, electro-, photodynamic-, laser and intralesional therapies have been limited by inconsistent efficacy, inconvenience, or toxicity. In this open-label phase 1/2 clinical trial, submicron particle paclitaxel in an anhydrous base (SOR007) was evaluated for topical treatment of CM from breast cancer (n=21), leiomyosarcoma (n=1) and Paget’s disease (n=1). Previously, in vitro, in vivo, and clinical studies demonstrated penetration of paclitaxel into the dermis with the silicone-based anhydrous producing subtoxic plasma levels in GLP toxicology studies and early clinical trials. Trial Design: The phase 1/2 open label trial evaluated 3 doses of SOR007 (0.15%, 1.0%, 2.0%). Approximately 0.5 grams (1 FTU) of SOR007 per 50 cm2 treatment area was applied BID during a 3+3 dose-rising phase for 28 days (n=10) or a dose-expansion phase at 2% strength BID for 28 days (n=2) or 56 days (n=11) unless discontinuation became necessary due to clinical course of the underlying disease. Results: At least one eligible lesion was treated per subject and classified per RECIST 1.1. In the 28-day application group, 10 subjects were treated and in the 56-day application group, 11 subjects were treated. Lesion response is summarized in the table below for data to date. Lesion response was evaluated within 2 weeks of last treatment day in most subjects. Conclusions: SOR007 was safe when applied to CM lesions. SOR007 resulted in decreased lesion progression or reduced lesion area in the majority of CM subjects. These clinical benefits became more consistent and pronounced at 2% strength with longer treatment suggesting a dose/duration response. Lesion pain reduction is also suggested from the study. Additional clinical research with more subjects and longer treatment periods is in the early planning stage. Lesion ResponseLesion response by SUBJECTLesion response by SUBJECTLesion response by INDIVIDUAL LESIONLesion response by INDIVIDUAL LESIONDose-rising 0.15%, 1%, 2% & Dose expansion 2%Dose-expansion 2%Dose-rising 0.15%, 1%, 2% & Dose expansion 2%Dose-expansion 2%BID x 28 daysBID x 56 daysBID x 28 daysBID x 56 daysN (subjects or lesions)8111823Complete Response0% (0/8)9.1% (1/11)5.5% (1/18)26% (6/23)Objective Response Rate13% (1/8)45% (5/11)17% (3/18)43% (10/23)No lesion progression in evaluable subjects 63% (5/8)82% (9/11)61% (11/18)83% (19/23) Citation Format: Mario E Lacouture, Julie E Lang, Sant Chawla, Shari Goldfarb, Alina Markova, Alexander Pan, Rose Marie Cavanna-Mast, Peter Mast, Christopher Savoie, Gere diZerega. Phase 1/2 clinical trial of a topical submicron particle paclitaxel (SOR007) for the treatment of cutaneous metastases [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-05.

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12100 Background: Rash associated with increased peripheral eosinophils develops in approximately 50% of metastatic breast cancer patients receiving alpelisib. Antihistamines and corticosteroids have limited benefit. Refractory rash may lead to decreased dose intensity and affect clinical outcome. Benralizumab is an anti-IL-5Rα chimeric monoclonal antibody that depletes peripheral eosinophils and has demonstrated benefit in eosinophilic asthma and hypereosinophilic syndrome. We investigate the efficacy and safety of benralizumab for the treatment of alpelisib rash. Methods: We performed a single-center, single-arm, prospective phase 2 study to evaluate the efficacy and safety of benralizumab in cancer patients who developed CTCAE grade 2/3 skin events resulting from immunotherapy or targeted therapies with absolute blood eosinophil counts of ≥300/mcl. While remaining on culprit drugs, patients were treated with benralizumab 30mg once every 4 weeks for the first 3 doses followed by once every 8 weeks for 3 additional doses (approved dosing for eosinophilic asthma). Primary endpoint was clinical response measured as reduction in CTCAE grade 2/3 skin event to grade ≤1 by week 4. Secondary endpoints were patient quality of life (QoL) measured by skindex16, safety data, need for supportive oral corticosteroids, and changes in cytokines and eosinophil biomarkers. This interim analysis focuses on patients with PIK3CA-mutant metastatic breast cancer receiving alpelisib. Results: Between September 16th 2020 and January 1st 2022, we enrolled 10 metastatic breast cancer patients with grade 2/3 rash attributed to alpelisib (5 pts with G3). All patients had a reduction of rash to grade ≤1 (n = 10, p < 0.0001), and a decrease in peripheral absolute eosinophils (mean 500/mcl to 0, p < 0.0001). Of these, 6 patients had been on prophylactic oral antihistamines and 2 had oral steroid coadministration. QoL significantly improved (Skindex16 mean score 58 to 16, p = 0.0001) and eosinophils in skin histology decreased per HPF (mean 6.25 to 0.25, n = 8, p = 0.2) by week 4. An increase in IL-5 > 600% and reduction IL-6 and TNF-α > 50% were reported by week 4 and 8. Grade 1/2 mucositis in 4 patients were reported as adverse events. Conclusions: Our findings suggest that benralizumab is safe and effective for the treatment of grade 2/3 rash with eosinophilia related to alpelisib in patients with breast cancer. A reduction in rash severity was evidenced in all patients, along with improved QoL. Larger controlled studies are in development to evaluate the efficacy of benralizumab for the prevention of alpelisib rash. Clinical trial information: NCT04552288.