PowerPoint Presentation A prospective clinical utility study demonstrates that physicians use the 40-gene expression profile (40-GEP) to guide clinical management decisions for Medicare-eligible patients with cutaneous squamous cell carcinoma (cSCC) Matthew S. Goldberg, MD1,2; Jennifer J. Siegel, PhD2; Kelli Ahmed, PhD2; Sarah J. Kurley, PhD2; Aaron S. Farberg, MD3 1Ichan School of Medicine, NY 2Castle Biosciences, TX 3Baylor Scott & White Health System, TX Background › The 40-GEP has demonstrated both analytical and improved clinical validity for risk stratification when compared to current staging systems, categorizing patients as low (Class 1), moderate (Class 2A), or high (Class 2B) risk for regional or distant metastasis within 3 years of diagnosis. 1-3 › Previously reported clinical utility studies of the 40-GEP test have demonstrated its use in directing personalized risk-aligned patient management, inclusive of: follow-up, surveillance imaging, sentinel lymph node biopsy, and adjuvant radiation therapy 4-8 (Table 1). This study was sponsored by Castle Biosciences, Inc. (CBI), which provided funding to the contributing centers for tissue and clinical data retrieval. JJS, SJK, KA, and MSG are employees and options holders of CBI. ASF is a consultant for CBI. References Results Presented at Fall Clinical Dermatology Conference, October 20-23, 2022, Las Vegas NV For more information: skurley@castlebiosciences.com › In this ongoing, prospective Clinical Utility and Health Outcomes Study (UTILISE), Analysis 1 showed that for more than 80% of patients under study, clinicians reported that the 40-GEP had a positive impact toward managing their high-risk SCC patient (i.e., increased confidence in treatment plan, risk-aligned changes, and patient more on board). › The 40-GEP impacts physicians’ assessment of risk for their patients with cSCC, which, in line with guidelines, is driving risk-aligned changes in treatment plans. › The clinical actionability rates of the 40-GEP for cSCC are comparable to those of currently covered molecular tests for cancer patients, such as those GEP tests for breast, prostate, and lung cancer. Conclusions Disclosures Methods Scan here for more info Feature n (%) Age (range) 65-90* Male 38 (64.4) Location on Head or Neck 43 (72.9) Patient immunosuppressed 2 (3.4) Neurologic symptoms at tumor site 1 (1.7) Chronic inflammation at tumor site 2 (3.4) Tumor diameter ≥2cm 21 (35.6) Rapidly growing tumor 6 (10.2) Poorly defined borders 10 (17.2) Poor differentiation 1 (1.7) Depth of Invasion** Beyond subcutaneous fat 1 (1.7) Clark level IV or V 18 (30.5) Breslow’s Thickness ≥2mm 3 (5.1) Lymphovascular invasion 1 (1.7) Perineural invasion 2 (3.4) 40-GEP Result*** Class 1 52 (88.1) Class 2A 7 (11.9) *To maintain confidentiality, any age over 89 was reported as 90 **Investigators were allowed to report depth of invasion using various options ***No Class 2B risk scores were observed at the time of analysis Table 2. Patient demographics (n=59) of the Medicare-eligible cohort Figure 3. The 40-GEP result is the most influential factor impacting clinicians’ management plans for 42% of patients *Clinicopathologic factors as choice options: tumor size, location, depth, differentiation status, histological subtypes, perineural or lymphovascular invasion, immune status, patient age, history of cSCC, medical history Figure 1. Design of UTILISE: a prospective, multi-center clinical utility study Table 1. Previously reported clinical utility studies support personalized risk-aligned changes in overall management plans after 40-GEP testing from clinicians treating high-risk cSCC patients Study Design Cohort (n) Findings Teplitz, et al. 2019 Prospectively designed study to determine impact of 40-GEP on recommended patient management strategies 402 clinicians (3 patient vignettes) 40-GEP test can significantly impact dermatologist management recommendations while remaining within the context of established guidelines. 4 Farberg, et al. 2020 Retrospectively designed study integrating 40-GEP into NCCN recommendations for patient management 300 patients Patients were risk-aligned with low, moderate, or high intensity management plans based on 40-GEP Class results. 5 Litchman, et al. 2020 Prospectively designed study to determine impact of 40-GEP on recommended patient management strategies 162 clinicians (2 patient vignettes) The 40-GEP test results influenced changes in clinical management decisions for high-risk SCC patients in a risk- appropriate manner while remaining within established guidelines. 6 Au, et al. 2021 Case reports of patients retrospectively tested with 40-GEP 2 patients The utility of the 40-GEP test to provide additional information for guiding patient management decisions and improving outcomes is demonstrated by two cases with identical tumor staging, yet divergent outcomes. 7 Hooper, et al. 2022 Prospectively designed study to determine impact of 40-GEP on recommended patient management strategies 34 real-world clinicians (6 real-world patients) The incorporation of the 40-GEP Class result had a significant impact on recommended patient management plans in a risk-appropriate manner while adhering to established guidelines. 8 1. Wysong, et al JAAD 2021 2. Ibrahim, et al Future Oncol 2021 3. Borman, et al Diagn Pathol 2022 4. Teplitz, et al JDD 2019 5. Farberg, et al CMRO 2020 6. Litchman, et al CMRO 2020 7. Au, et al Dermatol Ther 2022 8. Hooper, et al Cancer Inv 2022 9. Soliman, et al BMC Cancer, 2020 10. Martin, et al Curr Med Res Opin, 2015 11. Asad, et al Am J Surg, 2008 12. Gore, et al Cancer, 2017 13. Basourakos, et al, Front. Oncol, 2021 14. Lee, et al, Chest, 2021 Clinical Issue and Objective Management decisions for cSCC patients are determined by the clinician’s evaluation of the risk of disease progression. Contributing to the challenge for implementing risk-appropriate patient management are the limitations of staging systems and treatment guidelines in predicting poor outcomes. A prognostic 40 gene expression profile test (40-GEP) has been validated to accurately stratify risk for metastasis in patients with one or more high risk factors.1-3 The objective of this ongoing prospective study is to capture the impact of 40-GEP testing on clinician recommendations and actions for patients for clinical management of their cSCC undergoing testing as part of their clinical care. *n=3 cases with missingness and risk factor count of zero. Physician attested to eligibility for testing. P a ti e n ts ( % ) Risk Factor Count* Figure 2. Clinicopathologic risk factor count for cohort › During an ongoing multi-center, prospective study (UTILISE: Clinical Utility and Heath Outcomes Study of the prognostic 40-GEP test) clinician recommendations for patient management were recorded before and after 40-GEP testing, along with patient clinicopathologic factors, test results, and clinical management. › Analysis 1 consists of 11 private practice clinicians, comprised of Mohs surgeons (n=7), dermatologists (n=1), and physician assistants (n=3). › For the lead-in phase, physicians fill out a treatment plan assessment after ordering the 40-GEP test but before receipt of results for 5 patients. Details of patient management and outcomes are then collected at six-month intervals for three years. › Then, clinicians enroll patients into the clinical utility phase which will include the addition of a second questionnaire to complete after receipt of 40-GEP results. Details of any changes in patient management will be tracked along with patient outcomes, including metastasis-free survival, for all patients every six months for three years. › This Analysis 1 of the clinical utility phase of Medicare-eligible patients enrolled in the study are reported here (n=59). 1 2 3 4 0 10 20 30 40 50 What is the patient’s risk of developing nodal or distant metastasis? Pre-GEP Post-GEP n % of Class 1* Pre-GEP Post-GEP n % of Class 2A 5-10% <5% 12 23.5% <5% 10-30% 3 42.9% 10-30% <5% 1 2.0% 5-10% 10-30% 2 28.6% What is the overall management recommendation for this patient? Moderate Low 8 15.7% Low Moderate 3 42.9% Moderate High 1 14.3% Class 1 40-GEP aligned decrease in risk perception and treatment Table 3. Clinicians’ perception of metastasis likelihood and overall management intensity changes with 40-GEP results No impact on treatment plan or confidence No change in treatment plan, but patient is more on board Increased Clinician Confidence Made changes based on 40-GEP result 24% 24 % n=58* 59 % n=59 *n=1 case with no response 40-GEP Clinicopathologic factors* Lead-in Phase 40-GEP Results Received Clinical Utility Phase Enrollment Clinician Fills Out Pre-test Treatment Plan Clinician Fills Post- test Treatment Plan Outcomes and Data Collection every 6 months for 3 years Outcomes and Data Collection every 6 months for 3 years Clinician successfully completes enrollment of ≥5 high-risk cSCC patients Enrollment Clinician Fills Out Pre-test Treatment Plan 40-GEP Results Received *n=1 case with no response Class 2A 40-GEP aligned increase in risk perception and treatment Figure 4. The 40-GEP result positively impacted patient management in over 80% of patients 42% Most influential factor 58% 15% 59%2% Impact of 40-GEP Prognostic GEP test (Cancer) Intended Use Overall change in management 40-GEP (cSCC) To guide treatment decisions in patients with cSCC with one or more high-risk factors 24% 70-GEP (breast) To guide therapy decisions in patients with early-stage breast cancer9 24% 50-GEP (breast) To guide adjuvant treatment selection in patients with early-stage breast cancer10 20% 21-GEP (breast) To guide adjuvant treatment selection in patients with early-stage breast cancer11 44% 22-GEP (prostate) To guide decisions about adjuvant radiation therapy12 18% 17-GEP (prostate) To guide treatment decisions, including active surveillance, prostatectomy, and radiation therapy13 18% 23-GEP (lung) To guide invasive procedures, including surgery and surveillance in low/intermediate risk of lung malignancy14 25% Table 4. Overall management change in patients tested with the 40-GEP compared to commonly used prognostic GEP tests in other cancers https://castlebiosciences.com/research-development/publications/