Health-related quality of life in patients with metastatic Merkel cell carcinoma receiving second-line or later avelumab treatment: 36-month follow-up data

Abstract

Abstract Background In the single-arm, open-label, multicentre, international phase II trial (NCT02155647 Part A), metastatic Merkel cell carcinoma (mMCC) patients received second-line or later avelumab 10\xa0mg/kg every two weeks. Health-related quality of life (HRQoL) was assessed using the skin cancer-specific FACT-M and the generic EQ-5D. We report HRQoL results 36 months after enrolment of the last patient with focus on HRQoL deterioration-free survival (QFS) rates. Methods HRQoL data were obtained at baseline, week 7, and every 6 weeks until disease progression and/or treatment discontinuation. QFS was defined as the time interval between first dose and HRQoL deterioration event i.e. when a HRQoL domain score (FACT-M/EQ VAS) decreased from baseline equivalent to the minimal important difference (MID) threshold, with no further improvement thereafter. For sensitivity analyses, two thresholds are applied termed as minimum and maximum MID. QFS rates were derived from Kaplan-Meier curves and could be interpreted as the likelihood of a patient to endure a time period without relevant HRQoL deterioration until a certain time point. Results Based on the intention-to-treat population (n\xa0=\xa088), QFS rates ranged from 40.6% (FACT-M functional well-being, FWB) to 56.3% (EQ VAS) at 12 months when applying minimum MIDs (Table). At 36 months, rates ranged from 20.7% (FWB) to 37.7% (FACT-M social well-being). When applying the maximum MID, QFS rates ranged from 48.6% to 64.9% at 12 months, and 25.3% to 42.7% at 36 months. Conclusions As expected, QFS rates decreased over time; however, in the context of an aggressive cancer such as mMCC, various HRQoL domains show promising QFS rates suggesting a substantial proportion of patients reported stable or improved HRQoL on treatment with avelumab across time points, aligned with the clinical efficacy results throughout the long study follow-up of over 36 months. Table . 1320P HRQoL deterioration-free survival rates (QFS) by time interval (12, 24, 36 months) based on EQ VAS and FACT-M scores applying (negative) minimum/maximum Minimal Important Difference (MID) thresholds, ITT population (N\xa0=\xa088) MID thresholds 1 (min./max.) HRQoL deterioration-free survival rates (%) Minimum MID Maximum MID Month 12 Month 24 Month 36 Month 12 Month 24 Month 36 EQ-5D EQ VAS -7 / -10 56.3 47.4 34.8 59.0 45.5 38.5 FACT-M Physical well-being (PWB) -1 / -3 46.7 43.0 36.4 52.6 46.1 35.8 Social/Family well-being (SWB) -1/ -3 44.0 37.7 37.7 49.5 49.5 40.5 Emotional well-being (EWB) -1 / -3 49.2 41.0 32.8 55.9 51.2 42.7 Functional well-being (FWB) -2 / -4 40.6 32.6 20.7 52.8 48.5 33.6 Melanoma subscale (MS) -2 / -5 49.7 45.7 37.4 64.9 49.1 38.2 Melanoma surgery scale (MSS) -2 / -3 51.4 51.4 36.7 48.6 48.6 34.7 Trial Outcome Index (TOI) -4 / -9 50.4 38.2 31.2 61.2 42.1 32.7 FACT-G Total Score -4 / -8 46.8 37.7 24.0 51.7 43.4 27.6 FACT-M Total Score -5 / -12 46.6 37.6 23.9 56.9 39.7 25.3 1 Published in Bharmal, et al. (2017). Psychometric properties of the FACT-M questionnaire in patients with Merkel cell carcinoma. Health Qual Life Outcomes 15(1): 247. Legend: HRQoL=Health-Related Quality of Life; QFS=HRQoL deterioration-free survival rate; MID=Minimal Important Difference; ITT=Intention-to-treat population; VAS=visual analogue scale; EQ VAS=VAS of the EQ-5D questionnaire Clinical trial identification NCT02155647. Legal entity responsible for the study Merck Healthcare KGaA. Funding This study was sponsored by Merck Healthcare KGaA, Darmstadt, Germany, and is part of an alliance between Merck Healthcare KGaA, Darmstadt, Germany and Pfizer Inc., New York, NY, USA. Disclosure S.P. D’Angelo: Advisory / Consultancy: Incyte; Advisory / Consultancy: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar; Advisory / Consultancy: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: EMD Serono; Advisory / Consultancy: GSK; Advisory / Consultancy: ImmuneDesign; Travel / Accommodation / Expenses: Adaptimmune. S. Nolte: Full / Part-time employment, Employee of ICON plc, which is a paid consultant to the study sponsor: ICON plc. M. Schlichting: Full / Part-time employment: Merck Healthcare KGaA. M. Henry-Szatkowski: Full / Part-time employment, Employee of ICON plc, which is a paid consultant to the study sponsor: ICON plc. M. Hennessy: Full / Part-time employment: EMD Serono, Inc. M. Bharmal: Full / Part-time employment: Merck Healthcare KGaA.