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TPS741 Background: Hand-foot skin reaction (HFSR) is associated with the use of multi-targeted tyrosine kinase inhibitors sharing vascular endothelial growth factor receptor inhibitor (VEGFRi) activity (e.g., cabozantinib, regorafenib, sorafenib, sunitinib). HFSR results from impaired vascular repair mechanisms from inhibition of VEGF signaling and is characterized by painful palmoplantar lesions that may impact the quality of life and consistent dosing of anticancer agents. NOVA-II is a two-part, double-blind, randomized controlled trial evaluating OQL011, a nitroglycerin (NTG) topical ointment. Part 1 enrolled 31 subjects and studied OQL011 0.2% NTG for Grade ≥2 NCI CTCAE v5.0 palmar-plantar erythrodysesthesia (PPE). Part 1 safety and pharmacokinetic data support the continuance of NOVA-II, Part 2 dose-ranging study. The Part 1 inclusion criteria and primary endpoint were based on NCI CTCAE PPE. A unique investigator global assessment (IGA) was evaluated in Part 1 for HFSR severity (Grades 0-4) and has been revised utilizing Part 1 data for use as the primary endpoint for Part 2. We hypothesize that OQL011 containing NTG, a nitric oxide donor releasing free nitric oxide and activating guanylate cyclase in skin vessels, will mitigate HFSR symptoms and disease severity via local upregulation of the VEGF/VEGFR signaling pathways. Methods: NOVA-II Part 2 is a global, dose-ranging phase 2, double-blind, randomized controlled trial to evaluate the safety and efficacy of 3 doses of OQL011 (0.1%, 0.2%, and 0.5% NTG) compared to vehicle control for the treatment of moderate to severe VEGFRi associated HFSR. Part 2 will enroll up to 140 patients (randomized 1:1:1:1; vehicle: OQL011@ 0.1%: 0.2%: 0.5% NTG) with IGA Grade ≥3 (IGA scale 0-4). Subjects will apply the study drug (i.e., OQL011 or vehicle) to palmar and plantar surfaces TID and will be evaluated at Visit 1 (Day 0), Visit 2 (Day 14), and Visit 3 (Day 28). The primary endpoint is the proportion of patients achieving an IGA Grade ≤1 at Visit 2 (Day 14). A superiority test will be performed to compare each of the OQL011 doses to the vehicle, and the study drug exposure-response relationship will be explored. The correlation between IGA and NCI CTCAE v5.0 PPE, patient-reported outcomes including a numerical pain rating scale (NPRS), and Hand-foot Quality of Life (HF-QoL) questionnaire will be measured. Pharmacokinetics will be evaluated in a subset of subjects randomized 2:2:2:1, with 6 patients in each of the 3 OQL011 dose level groups and 3 patients in the vehicle group. PK samples will be collected on Day 0 at pre-dose, 5 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, and 8 h, after the first application of investigational drugs. Study enrollment for Part 2 is currently ongoing in the United States, India, and China. (NCT04088318) Clinical trial information: NCT04088318 .

422 Background: ALP is a PI3Kα inhibitor and degrader approved with fulvestrant for the treatment (tx) of patients (pts) with PIK3CA-mutated, HR+, HER2– ABC. Hyperglycemia (HG) and rash are expected adverse events with ALP tx and remain a challenge for physicians and pts. Management guidance is primarily based on clinical trial experience, which is not necessarily reflective of real-world pts. Here we report guidance for optimizing prevention and management of HG and rash in pts taking ALP based on an integrated Delphi panel, a systematic, validated approach to organize consensus from experts in the absence of definitive evidence. Methods: Two modified Delphi panels were conducted, focusing on HG and rash, respectively. Each panel included 4 oncologists, 4 endocrinologists or dermatologists, 1 clinical pharmacist, and 1 pt advocate. Experts were asked to rate appropriateness of 908 interventions for HG and 348 for rash on hypothetical pt scenarios on a 1 (highly inappropriate) to 9 (highly appropriate) scale. Results were reviewed at virtual meetings, after which experts repeated the rating. The level of agreement or disagreement was determined using the median scores and dispersion from the final rating, and this level of agreement was used to develop consensus statements and tx algorithms. Results: Per the HG panel, (a) ALP tx is appropriate in individuals with HbA1c 6.5% to < 8% with a pre-tx endocrinology consult; (b) low carbohydrate diet is appropriate in all pts starting ALP; (c) prophylactic metformin is appropriate in pts with baseline HbA1c 5.7%-6.4%; may also be appropriate in pts with HbA1c < 5.7%; (d) after metformin, an SGLT2 inhibitor or a thiazolidinedione is an appropriate second-/third-line anti-HG agent (or first-line in metformin-intolerant pts), while insulin is not. Per the rash panel, (a) prophylactic nonsedating (NS) H1 antihistamines (standard dose) are appropriate for all pts; (b) starting/escalating NS H1 antihistamines and topical steroids (TS) is the preferred first step for managing rash; (c) it is appropriate to add, but not replace with, a sedating H1 antihistamine, if response to high-dose, NS option is inadequate, and to add an H2 antihistamine if response is still inadequate; (d) it is appropriate to hold ALP and start oral corticosteroids (OCS) if rash affects > 30% body surface area and is recurrent or has moderate/severe symptoms; (e) if angioedema is present, it is appropriate to either hold ALP and start OCS, or permanently discontinue ALP tx. Conclusions: Until further evidence is available, these expert recommendations provide guidance on prevention and management of HG and rash related to ALP tx in routine clinical practice.

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.

TPS1113 Background: Breast cancer is the most common malignancy among women in the U.S. and is a leading cause of cancer-related death. Among women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, 45% harbor activating mutations in the PIK3CA gene , which induces hyperactivation of phosphatidylinositol 3-kinase (PI3K) and drives cell growth and survival. The SOLAR-1 trial found that the combination of alpelisib, a PI3K inhibitor, and fulvestrant, an endocrine therapy, significantly improved progression-free survival compared to fulvestrant alone, leading to Food and Drug Administration approval in PIK3CA-mutated metastatic breast cancer. While PI3K inhibition induces apoptosis of cancer cells, inhibition of this pathway in the liver and skeletal muscle impairs physiologic insulin signaling leading to hyperglycemia. This affects > 60% of patients, results in grade 3-4 hyperglycemia in 36% of patients, and is a major cause of interrupted/reduced dosing or discontinuation. In preclinical models, application of a very low carbohydrate (ketogenic) diet or a sodium-glucose cotransporter 2 inhibitor (SGLT2i), a commonly used diabetes medication, minimized hyperglycemia and improved the anti-tumor efficacy of PI3K inhibition. These interventions are safe and feasible in cancer patients but have not been studied for the prevention of PI3K inhibitor-associated hyperglycemia. Methods: We are conducting a multicenter phase II clinical trial (NCT05090358) in patients receiving standard-of-care alpelisib plus fulvestrant to test the efficacy of three interventions (n = 106): 1) ketogenic diet, 2) low-carbohydrate diet, or 3) canagliflozin (a SGLT2i) in preventing alpelisib-associated hyperglycemia. The goal of this study is to mitigate a major toxicity of PI3K inhibitors and maximize their clinical efficacy. Eligible patients must be postmenopausal and have histologically confirmed HR-positive, HER2-negative metastatic breast cancer, ≥1 activating PIK3CA mutations, measurable disease per RECIST v1.1 or at least one predominantly lytic bone lesion, recurrence or progression during or after endocrine-based therapy, ECOG performance status of 0-1, hemoglobin A1c < 8%, and fasting blood glucose < = 140mg/dL. Prior CDK4/6 inhibitor use is allowed. The primary endpoint is the grade 3-4 hyperglycemia-free rate at 12 weeks. Secondary endpoints include the 6- and 12-month overall response rate, 6- and 12-month progression-free survival, alpelisib adherence, changes in systemic hormones and metabolites related to glucose homeostasis, changes in body composition, and quality of life. The first patient was enrolled on October 15, 2021. Participating sites include Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, and the Ohio State University Wexner Medical Center. Clinical trial information: NCT05090358.

e19081 Background: Histiocytic neoplasms (HN) are clonal myeloid disorders with diverse clinical phenotypes. HN nearly invariably harbor mutations of the mitogen activated protein kinase (MAPK) pathway, including the BRAFV600E mutation in HN subtypes that are responsive to BRAF inhibition. More recently characterized, the second most frequently mutated gene driving HN is MAP2K1, with broad responsiveness to MEK inhibition reported. The most common MAP2K1 variant observed in our cohort (n=300 patients) is the exon 3 p.E102_I103 in-frame deletion, among the Class 3 MAP2K1 mutants predicted to be resistant to allosteric MEK inhibition. We present clinical and treatment characteristics of HN patients with Class 3 MAP2K1 mutations. Methods: Patients with HN and exon 3 p.E102_I103del or similar mutations identified by tumor sequencing were included. Sites of disease were captured. First- and later-line treatments were categorized as observation, chemotherapy (vinblastine, cytarabine, cladribine, methotrexate), immune modulation (anakinra or interferon), MEK inhibition (trametinib or cobimetinib), or ERK inhibition (ulixertinib). Clinical and radiologic responses were captured as partial response (PR), complete response (CR), or progressive disease (PD). PD includes relapse following PR or CR. Results: 16 patients were identified. 8 (50%) were female, and median age at HN diagnosis was 31 (range 22-58). 10 patients had Langerhans cell histiocytosis (LCH), 4 had Erdheim-Chester disease (ECD), 2 had mixed histiocytosis. Sites of HN were bone (16; 100%), lymph node (8; 50%), brain (8; 50%), skin/subcutaneous (4; 25%), retroperitoneum (3; 19%), cardiovascular (3; 19%), abdomen (2; 13%), reproductive (1; 6%) and other sites (5; 31%). Mutations identified were MAP2K1 p.E102_103del (13; 81%), p.L101_103delinsF (1; 6%), p.P105_I107delinsL (1; 6%), and p.I103_A106del (1; 6%). 2 (13%) patients had spontaneous regression of disease and were observed; 3 (19%) patients had CR to first-line chemotherapy. 3 (19%) patients have had CR/PR to first-line MEK inhibition. 8 (50%) patients had PD following chemotherapy and/or immune modulation; of those, 1 was lost to follow-up, 4 had CR/PR to MEK inhibition; however, 3 had PD despite MEK inhibition. These three patients and one treatment-naïve patient were treated with an oral ERK1/2 inhibitor, ulixertinib, on prospective protocols. 3 of 4 had a clinical or radiologic PR (1) or CR (2). Conclusions: Histiocytic neoplasms with Class 3 MAP2K1 mutations represent a diverse spectrum of disease characterized by frequent bone, nodal and neurologic involvement, by frequent resistance to chemotherapy. This entity is resistant to MEK inhibition in some patients, a phenomenon previously undocumented, and responsive to ERK inhibition, which may be a promising therapeutic approach to HN.

e24083 Background: EGFRi’s are associated with dermatologic AEs that include an acneiform skin rash. This rash occurs in up to 80% for all grades and 18% for grades ≥3. Treatments are based on grade and include topical antibiotics or corticosteroids for grades 1 and 2, and EGFRi dose interruption and/or oral corticosteroids for severe grades (i.e., ≥ grade 3). For prevention, topical corticosteroids or oral antibiotics are recommended. This survey was conducted to assess current toxicity management patterns and treatment gaps for EGFRi associated skin rash. Methods: An online survey (MedSurvey) with 5 eligibility & 8 questions related to EGFRi practice patterns was conducted (April 2021). Fifty-one practicing oncologists completed the survey. Results: Among the 51 oncologists, 86% have been practicing ≥ 11 yrs with 37% from an academic and 63% from a community setting. They (percent of respondents) prescribed cytotoxic chemotherapy (91%) and targeted agents (84%) > 10x/week. Prevention of EGFRi skin rash with topical antibiotics (33%), topical steroids (45%), and oral antibiotics (45%) were commonly administered prophylactic treatments, while 26% do not treat prophylactically. EGFRi’s were started at a lower dose always 6%, frequently (≥50%) 26%, sometimes (< 50%) 24%, and never 45% of the time. Skin rash treatment is started by 47% at Grade 1, 33% at Grade 2, and 2% ≥Grade 3, while 18% start treatment prophylactically. The majority (57%) would use a novel agent to treat skin rash, while 26% would use it for patients with a previous occurrence, 13% for those not responding to the standard of care and 2% would use this agent for selected EGFR inhibitors. For Grade 1 skin rash (multiple choices allowed), 33% used observation only for management, whereas 55% prescribed topical antibiotics, 35% prescribed oral antibiotics, and 55% used topical steroids. Dose reduction was implemented 4% of the time. For Grade 2 skin rash (multiple choices allowed) 51% used topical antibiotics, 63% prescribed an oral antibiotic, and 77% used topical steroids. Dose reduction was used 35% of the time. For patients not responding to standard therapy 6% switched to a different anti-cancer regimen, 16% changed to another EGFRi, while 77% interrupted the EGFRi therapy. Conclusions: Treating EGFRi-associated skin rash continues to be a significant challenge with Grade 2/3 toxicity or patients not responding to standard treatment. This often requires a therapeutic dose reduction or interruption that may impact the efficacy of anti-cancer treatment. Effective management (prevention and treatment) for skin toxicities associated with EGFRi inhibitors remains an unmet need for many patients and a treatment challenge for oncologists.

TPS2084 Background: Glioblastoma Multiforme (GBM), is the most common and aggressive brain tumor. Tumor Treatment Fields (TTFields) is a noninvasive, regional antimitotic treatment modality approved for the treatment of recurrent and newly diagnosed GBM by the US Food and Drug Administration. TTFields delivers low intensity (1-3 V/cm), intermediate frequency (100-300 kHz), alternating electric fields to the tumor through noninvasive transducer arrays placed on the skin, around the region of the body containing the tumor. During mitosis, TTFields disrupt the formation of the mitotic spindle during metaphase resulting in apoptosis. Dermatologic adverse events (AEs) to TTFields include dermatitis and infections and were reported in 54% of patients in a phase III trial. Topical triamcinolone and clindamycin have demonstrated anecdotal benefit because of their anti-inflammatory and antimicrobial activity. Pre-clinical studies have shown no negative effect on impedance when applied onto skin under the arrays. The effect of topical triamcinolone and clindamycin for the prevention of skin AEs to TTFields has not been studied prospectively. Methods: We are conducting a phase II multicenter clinical trial in patients receiving standard-of-care TTFields therapy for GBM to determine the efficacy of a prophylactic intervention: topical clindamycin 1% solution and triamcinolone 0.1% lotion in preventing grade ≥2 epicutaneous device-related events. Eligible patients must be ≥18 years of age, newly diagnosed with GBM and initiating TTFields within 7 days of study enrollment. The primary objective is to determine the effect of topical clindamycin 1% and triamcinolone 0.1% on the prevention of grade ≥2 device-related skin AEs. Secondary objectives include investigating the effect of study agents on skin-related quality of life (using the PRO-CTCAE modules for rash, ulcer, and pruritus), evaluating the efficacy of study agents applied to the scalp at every array change by standardized photography evaluated by a blinded investigator, measuring the duration of skin toxicities and usage of the TTFields device, measuring the duration of treatment interruptions and time to first grade ≥ 2 skin events, determining the bacterial flora of scalp infections, and determining the effect of study agents on TTFields’ impedance. Patients will be on study for 90 days. An end-of-study assessment will occur on day 90, and a post-treatment visit will occur on day 120. The first patient was enrolled on October 21, 2020 and hitherto, 8 patients have been consented. Participating sites include Memorial Sloan Kettering Cancer Center, Columbia University Medical Center, Tufts University Medical Center, Northwestern University, Washington University, University of Cincinnati, and John Theurer Cancer Center - Hackensack Meridian Health. Clinical trial information: NCT04469075.

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.

322 Background: VEGFRi therapies are associated with hand-foot skin reaction (HFSR) that affects up to 69% of patients depending on the VEGFRi administered. The incidence and severity of HFSR are dose-dependent and have been associated with improved clinical outcomes suggesting a direct toxicity mechanism. HFSR significantly diminishes patients’ quality of life and effects optimal treatment. Current HFSR treatments focus on managing symptoms since there are no effective therapies that address the underlying cause of HFSR. Small studies and expert opinion have suggested treating HFSR with topical corticosteroids or urea-based creams. However, the most effective management remains dose reduction/interruption or treatment discontinuation. This survey was conducted to assess current toxicity management patterns and treatment gaps for VEGFRi associated HFSR. Methods: An online survey (MedSurvey) with 5 eligibility & 8 questions related to VEGFRi practice patterns was conducted (April 27 to 30, 2021). Fifty-one (51) practicing oncologists completed the survey. Results: Among the 51 oncologists, 86% have been practicing ≥ 11 yrs with 37% from an academic setting and 63% from a community setting. They (percent of respondents) prescribed cytotoxic chemotherapy (91%) and targeted agents (84%) more than 10 times per week. Prevention of VEGFRi-induced HFSR with urea (57%) or topical steroids (75%) were the commonly administered prophylactic treatments. The majority (53%) would prophylactically use a novel agent to prevent HFSR, while 33% would use it for HFSR prevention in a patient with a previous occurrence, and 12% would use this agent for selected VEGFR inhibitors. Many oncologists (4% always, 61% sometime/frequently) start a VEGFRi at a lower dose and titrate up to prevent HFSR. For grade 1 HFSR (multiple choices allowed), 37% used observation only for management, whereas 51% prescribed urea ointment, and 63% used a topical steroid. Dose reduction was implemented 20% of the time. For grade 2 HFSR (multiple choices allowed) 53% used urea ointment, 84% prescribed a topical steroid and 59% considered dose reduction as a treatment strategy. For patients not responding to standard therapy 2% switched to a different anti-cancer regimen, 18% changed the VEGFRi, while 78% interrupted the VEGFRi therapy. Conclusions: Treating VEGFRi-associated HFSR continues to be a significant challenge with grade 2/3 toxicity or patients not responding to standard treatment. This often requires a therapeutic dose reduction or interruption that may impact the efficacy of anti-cancer treatment. Effective management (prevention and treatment) for skin toxicities associated with targeted-multikinase/VEGFRi inhibitors remains an unmet need for many patients and a treatment challenge for oncologists.

TPS396 Background: Hand-foot skin reaction (HFSR) is associated with the use of multi-targeted tyrosine kinase inhibitors sharing vascular endothelial growth factor receptor inhibitory (VEGFRi) activity (e.g., cabozantinib, regorafenib, sorafenib, sunitinib). HFSR affects the palms and soles with edema, erythema, hyperkeratosis, pain, and bullae/blisters impacting quality-of-life, activities of daily living, and consistent VEGFRi dosing. HFSR incidence differs among VEGFRi, ranging from 5-69% (all grades) and 1-19% (grade 3). Topical urea has marginal benefit, and to date, there are no regulatory authority approved HFSR treatments. The pathogenesis of HFSR has been partially associated with impaired vascular repair mechanisms resulting from inhibition of VEGF signaling. Nitric oxide (NO) has been reported to induce VEGF upregulation at a moderate concentration. We hypothesized that topical stimulation of VEGF signaling through OQL011, an NO donor, will safely and effectively mitigate HFSR. Methods: NOVA-II is a phase 2, double-blind, randomized vehicle-controlled trial evaluating the safety and efficacy of OQL011 for the treatment of moderate to severe HFSR. Subjects receiving a VEGFRi (either mono- or combination therapy) and have Grade ≥2 HFSR per NCI CTCAE v5.0 for palmar plantar erythrodysesthesia (PPE) were eligible. For Part 1, 31 subjects were randomized (2:1) and received 0.2% OQL011 topical ointment or vehicle TID for 6 weeks. The primary endpoint is the proportion of patients who achieve an NCI CTCAE v5.0 for PPE Grade 0 or 1 by Week 3. An investigator global assessment (IGA) scale is being developed to assess HFSR recovery, and a secondary endpoint will measure the proportion of patients who have improvement in HFSR severity and achieve an IGA score of clear (0) or almost clear (1) by Week 3 and/or Week 6. A Chi-square test will be used to detect a difference between the treatment arm and the vehicle-control arm. Additionally, the IGA score will be validated by assessing the inter- & intra-rater reliability. The correlation between IGA, NCI CTCAE v5.0 for PPE, and patient outcomes including Visual Analog Scale of Pain, HFSR Quality of Life questionnaire will also be reported. This study began enrolling patients in December 2019 and completed the last patient Visit in August 2021. Data lock, unblinding and data analysis will be completed by mid-November. Clinical trial information: NCT04088318.

e13548 Background: Accurate and comprehensive assessment of dermatologic adverse events (AEs) in clinical trials is challenging, given the heterogeneity of appearance and perception of these AEs. For dermatologic AEs, Common Terminology Criteria for Adverse Events (CTCAE) grading of clinical severity primarily relies on the clinician’s reporting of body surface area involved (BSA%) estimated by visual assessment combined with clinician’s interpretation of psychosocial impact, which can vary among raters. Although patient reported outcome (PRO-CTCAE) and QoL (SKINDEX-16) measures have been incorporated to improve accuracy and reliability of symptomatic AE evaluations, the subjective nature of dermatologic CTCAE grading remains. Clinical photography is routinely used to aid in visual comparison but cannot be incorporated to standardized measures due to inconsistencies in lighting, distance from the camera, and position. This prospective study aims to validate the accuracy and utility of affected BSA% using 3D-total body photography (TBP) and quantitative imaging analytics for standardized, objective assessment of immune-related cutaneous adverse events (ircAE) in clinical trials and/or prospective studies. Methods: Polarized and non-polarized TBPs (Canfield Vectra WB360) were acquired on two dermatology clinic visits 2-6 weeks apart (n = 8, to date). CTCAE, PRO-CTCAE, SKINDEX-16 were evaluated by one investigator for both visits. Image analysis including BSA% calculation was conducted using Vectra measurement software by an investigator blinded to clinical grades. Means and ranges for change in CTCAE, BSA%, and SKINDEX-16 were calculated. Results: To date, 29 patients with ircAE have been enrolled with 8 completing both visits. A greater improvement in affected BSA% (-1.9, -13.0, -20.1) and SKINDEX-16 (-8,-11.9,-19.5) were associated with a greater degree of clinical improvement measured by CTCAE (0 to -3). Widest range in the degree of change in BSA% (-24.4, -6.8) and SKINDEX-16 (-31,19) was observed in the group with intermediate change in CTCAE (-2 to -1, n = 5). Conclusions: Estimating affected BSA% via visual assessment is subject to human error and rely on memory or comparison with unstandardized photos to detect clinical improvement of dermatologic conditions. This poses a challenge particularly for cases with mild or moderate clinical improvement, demonstrated by the wide range in the degree of change for BSA% and SKINDEX-16. With consistent lighting, position, and objective measurements, 3D-TBP quantitative image analysis shows promise in reproducible, standardized monitoring and quantification of ircAE clinical severity. Furthermore, the quantitative nature of TBP measurement suggests its potential utility for correlation with underlying immunophenotyping correlative studies and clinical trials.

9092 Background: The optimal management for immune related adverse events (irAEs) in patients who do not respond or become intolerant to steroids is unclear. Guidelines suggest additional immunosuppressants based on case reports and expert opinion. Methods: We examined patients with advanced lung cancers at MSK treated with immune checkpoint blockade (ICB) from 2011-2020. Pharmacy records were queried to identify patients who received systemic steroids as well as an additional immunosuppressant (eg TNFα inhibitor, mycophenolate mofetil). Patient records were manually reviewed to examine baseline characteristics, management, and outcomes. Results: Among 2,750 patients with lung cancers treated with ICB, 51 (2%) received both steroids and an additional immunosuppressant for a severe irAE (TNFα inhibitor (73%), mycophenolate mofetil (20%)). The most common events were colitis (53%), pneumonitis (20%), hepatitis (12%), and neuromuscular (10%). At 90 days after start of an additional immunosuppressant, 57% were improved from their irAE, 18% were unchanged, and 25% were deceased. Improvement was more common in hepatitis (5/6) and colitis (18/27) but less common in neuromuscular (1/5) and pneumonitis (3/10). All patients with hepatitis received mycophenolate mofetil 500-1000mg BID for a median of 3 months, range 2-5 months. Of the 18 patients with colitis who improved with a TNFα inhibitor, 10 needed just one dose. Of 13 patients who died, 4 were related to toxicity from immunosuppression (3, infection-related deaths; 1, drug-induced liver injury leading to acute liver failure). Those who died from immunosuppressive therapy received higher amounts of systemic steroids than those who did not (max median 525 vs 132 mg prednisone equivalent, Mann Whitney U p = 0.004, total median 5.9k vs 2.3k mg prednisone equivalent, p = 0.004). Of 31 patients who received at least 3 weeks of prednisone ≥ 20mg, most (90%, 28/31) had at least one side effect that was brought to clinical attention (most commonly altered mood/ sleep, 52%, increase in BMI > 1kg/m2, 45%, and infection, 32%). Conclusions: Steroid-refractory/resistant immune related adverse events are rare. While existing treatments help patients with hepatitis and colitis, most patients with other irAEs remain refractory and/or experience toxicities from immunosuppression. Systemic steroid use likely contributed to side effects and mortality. A more precise understanding of the pathophysiology of specific irAEs is needed to guide biologically informed treatment regimens for severe irAEs to realize the true benefit of ICB therapy.

TPS12132 Background: Hand-Foot Skin Reaction (HFSR) is frequently associated with the use of multi-targeted tyrosine kinase inhibitors of the vascular endothelial growth factor receptor (VEGFRi) such as cabozantinib, regorafenib, sunitinib, and lenvatinib. HFSR affects the skin on the palms and soles and is manifested as edema, erythema, hyperkeratosis, and bullae, leading to a decrease in quality of life and interruptions in dosing. The incidence of HFSR differs among VEGFRi, ranging from 5-60% (all grades) and 1-18% (grade 3). To date, there is no FDA approved treatment for HFSR, and marginal benefit has been shown with topical urea or steroids. Although not fully elucidated, the pathogenesis of HFSR has been associated with impaired vascular repair mechanisms, caused by inhibition of VEGF signaling pathways. We hypothesize that topical stimulation of VEGFR through OQL011 will decrease the severity of HFSR symptoms via local upregulation of the VEGF/VEGFR related signaling pathways. Methods: NCT04088318 is a phase 2, double-blind, randomized controlled trial to evaluate the safety and efficacy of OQL011 compared to vehicle control in the treatment of moderate to severe HFSR in patients on VEGFRi therapy. Eligible patients will have ≥ grade 2 palmar plantar erythrodysesthesia (PPE). The study is expected to enroll 112 patients in two parts. In the first part, 42 patients will apply 0.2% OQL011 topical ointment or vehicle control (2:1 randomization) TID for six weeks. In Part 2, 70 subjects will be randomized into two additional dose levels or vehicle control in a 2:2:1 ratio. The two dose levels selected will be based on the efficacy and safety results of Part 1. The primary efficacy endpoint is improvement of NCI CTCAE v5.0 PPE to grade ≤1 by week 3. Photographs of the affected areas will be taken at Day 0, 7, 14, 21 and 42 timepoints. Superiority test will be performed to compare treatment groups, and the exposure-response relationship will be explored. In addition, an investigator global assessment (IGA) for HFSR will be used in this trial to specifically assess skin recovery and is proposed to be a new evaluation tool. The validity of IGA criteria will be evaluated by assessing the inter-rater and intra-rater reliability. The correlation between IGA, NCI CTCAE v5.0 for PPE, and patient reported outcomes including Visual Analog Scale of Pain, Hand-foot Quality of Life questionnaire will also be evaluated. This study began enrolling patients in December 2019 and is ongoing. Clinical trial information: NCT04088318.

12084 Background: Dermatologic toxicities from cancer treatments affecting patients from racial and ethnic minority backgrounds or skin of color (SOC) patients is an understudied area of research. These patients are also significantly underrepresented in therapeutic clinical trials, limiting complete understanding of toxicities associated with cancer therapies. Current treatment algorithms for dermatological adverse events (dAE) also do not take into account possible biologic differences in different skin types affecting toxicity presentation and treatment response. In this study we summarize the demographic, clinical, and treatment characteristics of oncology patients from racial and ethnic minority backgrounds who developed dermatologic adverse events related to cancer therapies. Methods: We performed a retrospective review of all SOC patients (Asian, Black, Hispanic) on active cancer therapy who received outpatient dermatology consultation at Memorial Sloan Kettering Cancer Center from January 1, 2014 to December 31, 2019. Electronic health record information for 2917 patients was obtained. A computational keyword-based text analysis of medical chart text, developed in consultation with a board-certified dermatologist, was performed to determine dermatologic diagnoses categories for each patient. All analyses were conducted using R statistical programming software, version 4.2.06. Results: There were 2917 outpatient dermatology consultations. Our population consisted of 1992 (68.29%) females and 925 (31.71%) males with a mean age of 53 (range 0-97). There were 35.55% Black, 41.28% Asian, 1.02% (30) Native American or Alaskan Native, 0.17% (5) Native Hawaiian or Other Pacific Islander. 729 were Hispanic ethnicity of which 641 were Caucasian. A total of 4,026 dermatologic diagnoses occurred in the study population. Bacterial infections were the most commonly observed, occurring in 15% of patients. Nail disorders were the second most common dAE, occurring in 14% of the study population, followed by eczema/eczematous reactions at 9%. In all racial groups, eczema/eczematous reactions, nail disorders, and dermatomyositis were in the top five most common observed dAEs. Asian patients made up the largest proportion of those who had morbilliform rash dAEs (55%) while Black patients made up the largest proportion of those with hyperpigmentation dAEs (54%) and vascular insufficiency dAEs (47%). Conclusions: The findings from our study indicate that pigmentary changes, bacterial infections, eczema/eczematous reactions, and nail disorders are the most common dAE types that occurred in our group of SOC patients. We hope to use this information to aid in the development of specific management strategies within the field of supportive oncodermatology to meet the needs of minority patient populations.

2632 Background: Immune-related cutaneous adverse events (irCAEs) are the most common and often the first toxicity of immune checkpoint inhibitors (CPIs). In the general population, irCAEs occur on average within 3.6 weeks of treatment initiation and most commonly manifest as maculopapular rash, lichenoid rash, and pruritus. Less is known about these irCAEs in racial and ethnic minority patients. The purpose of this study is to compare the irCAEs of cohorts of Caucasian and racial and ethnic minority patients at Memorial Sloan Kettering Cancer Center. Methods: Herein, we conducted a retrospective chart review of racial and ethnic minority patients treated with CPIs between 2012-2019 at Memorial Sloan Kettering Cancer Center. irCAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. These were compared to a Caucasian cohort matched by demographics and cancer therapy regimen. Results: One hundred ten racial and ethnic minority patients presented to dermatology for irCAEs. Our population consisted of 59 (53.6%) females and 51 (46.4%) males with a mean age of 59 (range 20-85). Of the patients who were seen by dermatology, 63/110 were Asian (57.3%) followed by 34/110 African American (30.9%), and 1 Native American. Twelve patients were of Hispanic ethnicity (10.9%), which included those of both African American and Caucasian race. The 110 patients that were evaluated by dermatology had 221 cutaneous adverse events. Rash (96, 43.4%), pruritus (40, 18.1%), and xerosis (23, 10.4%) were most frequently diagnosed (average time from treatment start to presentation was 125 days). Dermatology identified 87 (39.3%) grade 1, 103 (46.6%) grade 2, 30 (13.5%) grade 3, and 1 (0.4%) grade 4 events. There were 17 (15.5%) treatment interruptions, including 7 patients who required permanent discontinuation. In the Caucasian cohort, mean time to onset was 228 days (range 1-1500). Dermatology identified 48 (43.6%) grade 1, 44 (40.0%) grade 2, 18 (16.4%) grade 3, and 0 (0.0%) grade 4 events, with maculopapular rash (55, 50.0%) and pruritus (25, 22.7%) most frequently diagnosed. Conclusions: Our findings suggest that irCAEs occur frequently in cancer patients from racial and ethnic minority groups, with similar grade and morphology as Caucasian patients. When irCAEs develop in this population, the diagnosis occurred later than what has previously been reported, possibly due to these patients seeing MSK oncologists with an established dermatology consultation system and insight into how to manage these patients on their own. Prospective evaluation of underrepresented minorities receiving CPI therapy is warranted in order to identify risk factors and therapeutic strategies for these untoward events, so that optimal cancer care may be delivered.

1063 Background: Rash develops in approximately 50% of breast cancer patients receiving alpelisib, often requiring dose modifications. Herein, we describe the characteristics of alpelisib-related dermatologic adverse events (dAEs). Methods: A single center retrospective analysis was conducted via review of electronic medical records. We collected clinical, laboratory and management data relevant to patients treated with alpelisib for advanced breast cancer under four different randomized clinical trials or post approval by regulatory agencies from 6/1/2013 to 7/31/2019. Type and severity of dAEs was recorded using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Results: A total of 102 patients (mean age 56 years, range 27-83) receiving alpelisib from 200 to 350 mg daily, most frequently in combination with endocrine therapy (79, 77.5%) were included. We identified 41 (40.2%) patients with all-grade rash [CTCAE grade 1/2 = 22 (21.6%); CTCAE grade 3 = 19, (18.6%)] distributed primarily along the trunk (18, 78%) and developing, on average, within 12.8 +/- 1.5 days of treatment initiation (n = 38). Mean duration of rash was 7.1 +/- 3.8 days; and no grade 4 dAEs were observed. Of 29 patients with documented morphology of alpelisib-related dAEs, the majority (26, 89.7%) had maculopapular rash. Thirteen (68%) of 19 patients with any-grade rash and report of any associated symptoms had pruritus (7, 36%) or burning pain (6, 32%). All-grade dAEs correlated with an increase in serum eosinophils from 2.7% to 4.4% (p < 0.05), and prophylaxis with non-sedating antihistamines (n = 43) was correlated with a reduction of grade 1/2 rash onset (OR 0.39, p = 0.09). Sixteen (84.2%) of 19 patients with grade 3 dAEs had interruption of alpelisib, followed by management with antihistamines, topical and/or systemic corticosteroids. We did not observe rash recurrence in 12 (75%) of these 16 patients who re-initiated therapy; and the majority (9, 56.3%) were re-challenged without a dose reduction. Conclusions: Pruritus and increased blood eosinophils occur with maculopapular rash within the first two weeks of initiating alpelisib and persists for approximately seven days. To reduce onset of grade 1/2 rash, non-sedating antihistamines (i.e. cetirizine) are recommended during the first eight weeks. While grade 3 rash leads to interruption of alpelisib, dermatologic improvement is evident with systemic corticosteroids; and most patients can resume therapy at a maintained or reduced dose upon re-challenge.

e24126 Background: TTFields are low intensity, intermediate frequency, alternating electric fields applied continuously using 2 pairs of skin-affixed transducer arrays. TTFields are FDA-approved in GBM and mesothelioma. The most common TTFields-related adverse event (AE) is mild-to-moderate dermatitis (beneath arrays), via long-term irritant exposure and local hyperhidrosis and occlusion exacerbation. Skin reaction mitigation strategies may improve quality-of-life (QoL) and ensure usage, as maximal survival benefits have been correlated with duration of use. Not all skin care products are TTFields compatible and may increase electrical impedance and lead to beneath array temperature increases. The aim of this in vivo study was to investigate the effects of 62 commercially available skin care products on electrical impedance during TTFields treatment. Methods: TTFields (200 kHz; optimal GBM frequency) were applied to rats using transducer arrays made of the same ceramic disks and hydrogels used in patients with GBM. To test electrical impedance effects, skin care products were applied to the skin immediately before array placement. The change in impedance relative to naïve skin was measured using the Optune device. Sixty-two commercially available products from 8 groups (adhesive removers, antibiotics, antiperspirants, antiseptics, cleansers, moisturizers, skin barriers, and topical corticosteroids) were evaluated. Results: Most lotions, soaps, foams, and solutions had minimal effect on electrical impedance, while petrolatum-based ointments significantly increased electrical impedance. Conclusions: TTFields compatible skin care products that did not affect electrical impedance were identified from each of the 8 groups and could be considered for further evaluation. All petrolatum-based ointments that were tested led to an increase in electrical impedance and are thus not recommended. Local application of TTFields compatible skin care products should be prospectively investigated in the clinical setting for their potential role in minimizing TTFields–related skin AEs. The randomized, double-blind PROTECT (PROphylactic skin Toxicity thErapy with Clindamycin and triamcinolone in GBM patients Treated with TTFields) study, should help establish which products best reduce skin AEs in patients with GBM and assess impact on QoL.

3076 Background: The advent of immune checkpoint inhibitors (CPIs) for the management of advanced malignancies has led to unintended consequences of nonspecific immune activation. Cutaneous immune related adverse events (irCAEs) are the most common and first to manifest, on average within 3.6 weeks of treatment initiation. irCAEs may require CPI treatment dose reduction or discontinuation and negatively impact patient quality of life. There is substantial variability in the reporting of these toxicities and inadequate reporting in skin of color patients (SOC), who are often underrepresented in oncology clinical trials. The purpose of this study is to characterize irCAEs in SOC cancer patients. Methods: A single center retrospective analysis of electronic medical records from 2009-2020 was conducted. SOC was defined as African American, Hispanic, Native American/Pacific Islander, or Asian. irCAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Of 1459 SOC patients that presented to our institution and received CPIs during the study period, 175 (12%) presented to dermatology for irCAEs [African American (56, 32%); Asian (98, 56%); Hispanic (20,11%); Native American (1, 0.5%)]. Patients’ toxicities were stratified by CPI mechanism: anti-PD-1/L1 (139, 79%), combination of anti-PD-1/L1 plus anti-CTLA-4 (29, 17%), and anti-CTLA-4 therapy (7, 4%). Of 376 irCAEs, pruritus (62, 16%), xerosis (42, 11%), maculopapular rash (40, 11%), and cutaneous hyperpigmentation (36, 10%) were most frequently diagnosed. There were 86 (23%) grade 1, 93 (25%) grade 2, and 18 (5%) grade 3 events. Average time from CPI-treatment initiation to irCAE onset was 6.5 months (SD 7.9). Fifteen (9%) patients required CPI dose reduction or discontinuation due to skin toxicity. Topical corticosteroids (133, 76%) were the most frequently used treatment for all irCAEs. Conclusions: Our findings suggest that irCAEs occur frequently in SOC cancer patients. Furthermore, a 6.5-month delay in time to diagnosis highlights a need for increased surveillance of these cutaneous toxicities in darkly pigmented skin. Generally, SOC patients present unique diagnostic and management challenges due to differences in skin biology and propensity toward hyperpigmentation; however, in SOC cancer patients, the mechanisms of oncologic immunotherapy must be considered in developing successful treatment strategies and management of dermatologic health in this population.

12074 Background: Pigmentary disorders are known to disproportionately affect individuals with darker skin, including African Americans (AAs)— a historically underrepresented population in oncology research. However, reports on the prevalence and characterization of anticancer-therapy related cutaneous pigmentary changes in this population are lacking. Methods: A retrospective analysis of AA cancer patients that ever received a hematopoietic stem cell transplantation (HSCT) and/or systemic oncologic therapy within six months prior to diagnosis of cutaneous hypo- or hyperpigmentation at our institution between 4/18/2012 and 8/26/2019 was conducted. Clinical and management characteristics were summarized; severity of pigmentary changes was assessed using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v.5.0). Results: From a total of 1342 AA patients evaluated by oncodermatologists during the study period, 121 (9%) met inclusion criteria. Average age in this cohort was 52, and 102 (84%) were women. Breast (63, 52%), gastrointestinal (14, 12%), and hematologic malignancies (13, 11%) comprised the majority of cancer diagnoses. Most (93, 77%) patients had skin hyperpigmentation (84, 69%) or hypopigmentation (9, 7%) as a primary CTCAE diagnosis; the rest had secondary post-inflammatory hyperpigmentation (28, 23%). A higher proportion (105, 87%) of pigmentary alterations was attributed to single agents [i.e. chemo- (55, 46%), radiation (16, 13%), targeted (12, 10%), endocrine (9, 7%), and supportive oncologic (6, 5%) therapy] versus combination treatment (16, 13%). Five (4%) patients had graft versus host disease associated with allogeneic HSCT, four (80%) of which presented as cutaneous hypopigmentation. Hand foot syndrome (24, 20%), acneiform rash (24, 20%), and radiation dermatitis (16, 13%) were commonly diagnosed dermatologic adverse events (dAEs), generally classified as mild/grade 1 (67, 55%) in severity. For management, skin lightening agents +/- emollients (36, 30%) or emollients alone (25, 21%) were highly recommended. Topical corticosteroids +/- emollients were prescribed just as frequently as reassurance and/or avoidance of sun exposure (22, 18%). Conclusions: Cutaneous pigmentary changes related to cytotoxic chemotherapy, radiation and/or targeted oncologic therapy are common in AA cancer patients. Undertreatment of these dAEs, possibly due to under-recognition in darker skin, warrants further investigation to assess impact on quality of life and help improve management in this population.

e24086 Background: Nasal vestibulitis has been infrequently described as a side effect of cancer-directed therapy; however, a preliminary study reported that 71% of patients undergoing taxane chemotherapy experienced nasal vestibulitis symptoms. This natural history trial describes the incidence, characteristics, and severity of nasal vestibulitis symptoms among patients undergoing paclitaxel, docetaxel, and non-taxane chemotherapy. Methods: Eligible participants who reported baseline (prior to starting chemotherapy) nasal symptoms ≤ 2 on a 10-point scale were enrolled in this trial upon initiation of a new treatment regimen, involving paclitaxel or docetaxel, or non-taxane chemotherapy. Participants completed nasal symptom logs each time they received a dose of therapy until either the regimen was stopped or four months had passed. The proportion of patients reporting new nasal symptoms was estimated within each cohort with the 95% exact confidence interval (CI). A cumulative incidence model was utilized to quantify the incidence of treatment-emergent nasal symptoms within each cohort, while controlling for age, sex, smoking history, and history of asthma or allergies. Results: Thirty-five participants received paclitaxel, 21 received docetaxel, and 25 received other types of chemotherapy. 86.4% of participants were female, mean age was 60.2 ± 11.2 years; 93.8% of participants completed 2 or more surveys. A higher percentage of participants in the paclitaxel cohort experienced new nasal vestibulitis symptoms than participants in the other two cohorts. The percentage (95% CI) of participants with nasal symptoms, for patients receiving paclitaxel, docetaxel, and non-taxane chemotherapy were 74.3% (56.7%, 87.5%), 47.6% (25.7%, 70.2%), and 44.0% (24.4%, 65.1%), respectively. Epistaxis was reported by 60% of participants in the paclitaxel cohort. Paclitaxel-receiving participants also reported nasal dryness (48.6%), scabbing (40.0%), and pain (20.0%). Nearly half of participants reported moderate symptoms (4-7 out of a 10-point scale), with 8.6% reporting symptoms as severe (8-10 on a 10-point scale). Conclusions: Nasal vestibulitis is a common side effect of chemotherapy, especially paclitaxel chemotherapy.

e23063 Background: Clinical symptom is often a direct method to evaluate the treatment effects. With the emergence of EGFR-targeted drugs on market, it is unclear to apply cutaneous toxicity in evaluating treatment effects and outcomes in cancer patients. This study aimed to determine whether adverse skin event as a survival indicator for patients treated with EGFR tyrosine kinase inhibitors. Methods: PubMed, EMBASE, Scopus, trial register and Cochrane Library were searched on November 11, 2018 to identify studies reporting survivals outcomes. The following search/exploded terms were used: “ EGFR-TKIs: gefitinib/erlotinib/afatinib/osimertinib ”, “ cutaneous toxicity”, “ survival”. Two investigators performed study selection independently and assessed risk of bias with ROBINS-I method. Data were pooled with random effects models and further subgroup by cancer types. Funnel plot, Egger test and Begg test were performed for detection of publication bias. Sensitivity analysis was performed by excluding potential outliers. Results: There were 24 studies identified with 4696 patients included. Skin adverse event was found to be significantly associated overall survival rate (HR, 0.48; 95% CI, 0.43-0.53; P < 0.00001; I2 = 83%) and progression free survival rate (HR, 0.59; 95% CI, 0.41-0.85; P= 0.004; I2 = 88%). Subgroup analysis suggested among non-small cell lung cancer patients, skin adverse event was significantly associated with overall survival (HR, 0.39; 95% CI, 0.25-0.60; P < .0001; I2 = 86%) but not progression free survival (HR, 0.65; 95% CI, 0.29-1.45; P= 0.29; I2 = 95%). Among other cancer types patients, skin adverse event was significantly associated with overall survival (HR, 0.59; 95% CI, 0.41-0.84; P= 0.004; I2 = 70%) and progression free survival (HR, 0.61; 95% CI, 0.41-0.91; P= 0.02; I2 = 80%). Begg test and Egger test suggested no evidence of publication bias. Sensitivity analysis also showed similar results. Conclusions: Skin eruption had 52% lower risk of death and 41% lower risk of progression in cancer patients treated with EGFR-TKIs. This association should be further incorporated with cancer survivorship care planning.

e12537 Background: Cyclin-dependent kinase (CDK) 4 and 6 inhibitors are a novel therapy for metastatic breast cancer, and have shown to double the risk of alopecia. This study analyzed CDK4/6 plus aromatase inhibitor-induced alopecia (CDKIA), its impact on quality of life (QoL), and response to topical dermatologic therapy. Methods: The study analyzed a retrospective cohort of breast cancer patients diagnosed with CDKIA, evaluating clinical features, QoL, and response to therapy. CDKIA was also compared with endocrine-therapy induced alopecia (EIA). Results: 39 female CDKIA patients (median age 62 years [range 34-81]) were included, and 36 (92%) had standardized clinical images. CDKIA was most commonly attributed to a CDK inhibitor and letrozole in 23 patients (59%). CDKIA was similar to androgenetic alopecia (AGA) in every patient. Compared to EIA, CDKIA took less time to develop, was more severe, was associated with diffuse alopecia more frequently, and consisted of more vellus hairs on trichoscopy (Table). The Hairdex questionnaire, an alopecia-specific QoL survey, showed that CDKIA patients experienced worse QoL than EIA patients ( P < 0.05) and were most affected emotionally ( P < 0.01). There was a moderate to significant alopecia improvement in 11 of 13 CDKIA patients (85%) after treatment with topical minoxidil. Conclusions: CDKIA was clinically similar to AGA in association with diffuse alopecia. Patients with CDKIA had a negative emotional impact on appearance-based QoL. However, topical minoxidil may improve the severity of CDKIA. Baseline characteristics of CDKIA and EIA patients. [Table: see text]

11586 Background: Hand-foot skin reaction (HFSR) is the most common regorafenib adverse event. However, no intervention has demonstrated efficacy in preventing or palliating this adverse event, short of modulating the regorafenib dose. Methods: The Regorafenib Dose Optimization Study (ReDOS) was a randomized trial ( https://clinicaltrials.gov/ct2/show/NCT02368886 ); here we describe an a priori secondary analysis of ReDOS with the goal of assessing whether clobetasol 0.05% cream (a potent corticosteroid) applied to the palms and soles twice per day is more effective when prescribed pre-emptively (before the development of HFSR) versus reactively (after the development of HFSR). Patients were assessed during the 1st 2 cycles of regorafenib. Results: Among 116 evaluable patients, 61 received pre-emptive clobetasol, and 55 reactive clobetasol. Baseline demographics were comparable between groups. During the 1st regorafenib cycle, 46% and 52% of patients developed HFSR with pre-emptive and reactive clobetasol, respectively (p = 0.52). However, during the 2nd cycle, 56% (of 47 total patients) and 80% (of 41 total patients), developed this toxicity with pre-emptive and reactive clobetasol, respectively (p = 0.02). Of note, during the 2nd cycle, rates of grade 1,2, and 3 HFSR were 40%, 11%, and 4% (pre-emptive) and 45%, 25%, and 10% (reactive) (p = 0.07). A sensitivity analysis to examine rates of no HFSR over all 2 regorafenib cycles showed that no HFSR occurred in 33% (of 61 total patients) with pre-emptive clobetasol versus 15% (of 55 total patients) with reactive clobetasol (p = 0.02). Patient-reported outcomes showed HFSR compromised activities of daily living, including getting dressed, preparing meals, walking, and even driving, with seemingly worse descriptive outcomes in patients who received reactive therapy. No adverse events from clobetasol were reported. Conclusions: Compared to reactive therapy, pre-emptive topical clobetasol might lessen regorafenib-induced HFSR. Clinical trial information: NCT02368886.