Assessment of Quality of Life Using Skindex-16 in Patients With Locally Advanced Basal Cell Carcinoma Treated With Vismodegib in the STEVIE Study

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1 Assessment of Quality of Life Using Skindex-16 in Patients With Locally Advanced Basal Cell Carcinoma Treated With Vismodegib in the STEVIE Study Jean-Jacques Grob, 1 Karen Bartley, 2 Rainer Kunstfeld, 3 Brigitte Dréno, 4 Laurent Mortier, 5 Paolo Antonio Ascierto, 6 Caroline Dutriaux, 7 Nicolas Meyer, 8 Bernard Guillot, 9 Reinhard Dummer, 10 Sarah Williams, 11 Alberto Fittipaldo, 11 D. Scott Ernst, 12 Axel Hauschild, 13 Nicole Basset-Seguin, 14 Johan Hansson 15 1 Aix Marseille University Timone Hospital, Marseille, France; 2 Genentech, Inc., South San Francisco, CA, USA; 3 Medical University of Vienna, Vienna, Austria; 4 Nantes University, Nantes, France; 5 University of Lille 2, Lille Regional University Hospital, Lille, France; 6 Istituto Nazionale Tumori Fondazione G Pascale, Naples, Italy; 7 University Hospital of Bordeaux, Bordeaux, France; 8 Paul Sabatier University and Toulouse Cancer University Institute, Toulouse, France; 9 University Hospital of Montpellier, Montpellier, France; 10 University Hospital Zurich, Zurich, Switzerland; 11 Roche Products Ltd, Welwyn Garden City, UK; 12 Western University, London Regional Cancer Program, London, Ontario, Canada; 13 University Hospital Schleswig-Holstein, Kiel, Germany; 14 Université Paris Diderot Paris 7 and Hôpital Saint-Louis, Paris, France; 15 Karolinska Institutet, Stockholm, Sweden

2 Disclosures Dr. Grob declares the following conflicts of interest: Consulting/advising: Roche, GlaxoSmithKline, Bristol-Myers Squibb, Amgen, Merck, and Novartis Speakers bureau: GlaxoSmithKline Trial grants/research funding: Roche and Bristol-Myers Squibb This study was sponsored by F. Hoffmann-La Roche Ltd 2

3 Background STEVIE (ClinicalTrials.gov identifier, NCT ) is an ongoing phase 2 study to evaluate the safety of vismodegib in patients with labcc or mbcc 1 Skindex-16 assessments from an interim analysis of 499 patients of the efficacy-evaluable population with histologically confirmed disease are presented Objective To assess the disease burden related to BCC from the patients perspective using the Skindex-16 instrument Assessments were conducted at baseline, Cycle 2 Day 1, Cycle 7 Day 1, and end of study BCC, basal cell carcinoma; la, locally advanced; m, metastatic. 1. Basset-Seguin N et al. Lancet Oncol. 2015;16:

4 Study Design 1 mbcc labcc Vismodegib continual dosing 150 mg/day Until progression, intolerable toxicity, or withdrawal from study Safety follow-up Months 1, 3, 6, 9, and 12 Primary objective Safety Population size: 1200 patients planned 1232 patients enrolled Secondary objectives Overall response (based on RECIST), time to response, duration of response, progression-free survival, and overall survival HRQoL (as measured by Skindex-16) HRQoL, health-related quality of life; RECIST, Response Evaluation Criteria in Solid Tumors. 1. Basset-Seguin N et al. Lancet Oncol. 2015;16:

5 Effects of Skin Disease Skindex item patient-completed questionnaire whose items compose three domains (symptoms, emotional well-being, and functioning) Items are rated on a 7-point scale measuring the level of bother over the previous week, ranging from 0 (never bothered) to 6 (always bothered) Assessed at baseline, Cycle 2 Day 1, Cycle 7 Day 1, and end of study at a subset of clinical trial sites Decrease in score represents clinical improvement Clinically meaningful improvement defined as decrease of 10 points from baseline 1 Q, question. 1. Chren M-M et al. J Invest Dermatol. 2007;127: Symptoms (Q1-Q4) Itching Burning or stinging Hurting Being irritated Emotional Well-Being (Q5-Q11) Persistence/recurrence Worry Appearance Frustration Embarrassment Being annoyed Feeling depressed Functioning (Q12-Q16) Interactions with others Desire to be with people Show affection Daily activities Work or do what you enjoy 5

6 Patient Demographics labcc mbcc (n = 468) (n = 31) Male, % Mean age (years) ± SD 69.0 ± ± 12.9 Lesion location a n Head or neck, % Other, % BCCNS a n Yes, % Measurable disease n Yes, % a Reduced denominators are due to missing/unknown data. BCCNS, BCC nevus syndrome; SD, standard deviation. 6

7 Skindex-16 Scores at Baseline Items are rated on a 7-point scale measuring the level of bother over the previous week, ranging from 0 (never bothered) to 6 (always bothered) Responses to each item were transformed to a linear scale of 100, with higher scores indicating a greater level of bother (0 = never bothered, 100 = always bothered) Symptoms domain labcc (n = 455) mbcc (n = 29) Mean ± SD 22.9 ± ± 29.3 Median Emotional Well-Being domain Mean ± SD 47.9 ± ± 36.2 Median Functioning domain Mean ± SD 27.6 ± ± 30.8 Median

8 Median Skindex-16 Change From Baseline (points) Change in Emotional Well-Being Domain by labcc Subgroup Clinically meaningful improvements (decreases 10 points from baseline 1 ) in emotional well-being scores were observed across subgroups and time points No consistent differences were seen by gender and BCCNS status Improvements from baseline were consistently larger for patients with primary lesions in a location other than head/face or neck and for patients aged years This improvement was driven by large reductions in the level of bother related to the persistence/reoccurrence, worry, and appearance of patients skin conditions (data not shown) 0 Sex Emotional Well-Being Domain Age (years) BCCNS status Lesion location All patients Female Male >65 Yes No Head/neck Other 10 Clinically meaningful improvement Cycle 2 Cycle 7 EOS Cycle length = 28 days. EOS, end of study. 1. Chren M-M et al. J Invest Dermatol. 2007;127:

9 Median Skindex-16 Change From Baseline (points) Median Skindex-16 Score (points) Change in Symptoms and Functional Domains by labcc Subgroup Clinically meaningful deterioration 1 was not observed in either the symptoms or functioning domain in patients with labcc No clinically meaningful improvements 1 were seen for functional scores in patients with labcc (below) Symptoms Domain Functioning Domain Sex Age (years) BCCNS status All patients Female Male >65 Yes No 0 Lesion location Head/ neck Other Sex Age (years) BCCNS status All patients Female Male >65 Yes No 0 Lesion location Head/ neck Other Cycle 2 Cycle 7 EOS Clinically meaningful improvement Cycle 2 Cycle 7 EOS Clinically meaningful improvement Cycle length = 28 days. 1. Chren M-M et al. J Invest Dermatol. 2007;127:

10 Conclusions Skindex-16 scores at baseline indicate that patients with BCC experienced marked burden in their emotional well-being but were minimally bothered by how their BCC impacted their symptoms and functioning, suggesting that only the emotional well-being domain had a substantial impact on patients day-to-day lives at baseline Clinically meaningful improvements in emotional well-being were observed among patients with labcc at each postbaseline assessment; these improvements were driven by large reductions in the level of bother related to persistence/reoccurrence, worry about lesions, and appearance of lesions No consistent meaningful change, whether it be improvement or deterioration, was observed in the domains representing symptoms and functioning The sample size of patients with mbcc was limited; no meaningful improvement was seen at any time point across all domains Limitations Single-arm, open-label study Skindex-16 is a dermatology instrument that focuses on specific domains of disease burden as they relates to skin disease, but it does not comprehensively capture all relevant aspects of HRQoL (eg, treatment burden) Combined with the clinical efficacy data from this study, 1 the patient-reported findings from this large safety study support the effectiveness of vismodegib in the treatment of labcc 1. Basset-Seguin N et al. Lancet Oncol. 2015;16:

11 Acknowledgments We thank the investigators, patients, and current and past members of the Roche and Genentech vismodegib team Roche is developing vismodegib under a collaboration agreement with Curis, Inc. Vismodegib was discovered by Genentech and was jointly validated by Genentech and Curis through a series of preclinical studies Through this collaboration, Genentech (USA), Roche (outside the USA, excluding Japan and Korea), and Chugai Pharmaceuticals (Japan) are responsible for the clinical development and commercialization of vismodegib This analysis was funded by F. Hoffmann-La Roche Ltd. Third-party writing assistance for this poster was provided by ApotheCom (San Francisco, CA, USA) and was funded by F. Hoffmann-La Roche Ltd 11