Association Between Tumour Lesion Size and Health-Related Quality of Life Outcomes in Patients with Metastatic Merkel Cell Carcinoma Treated with Avelumab

OBJECTIVES: In patients with metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer, changes in tumour size during treatment may be associated with an impact on functioning and health-related quality of life (HRQoL). This research aimed to investigate this association. METHODS: Patients (N=88) with stage IV chemotherapy-refractory MCC receiving avelumab in a single-arm, open-label, multicentre, international phase 2 trial (NCT02155647) completed FACT-Melanoma (FACT-M) and EQ-5D-5L questionnaires at baseline, week 7 then every 6 weeks until week 25. FACT-M has been shown to perform adequately in the mMCC population. Tumour size was determined from radiological assessment every 6 weeks based on RECIST 1.1, and mapped onto HRQoL assessments occurring within 7 day proximity Associations were evaluated by linear regression of change in HRQpL on percent change in sum of target lesion size (SLD) at week 7 and all subsequent timepoints. Mean HRQoL score changes corresponding to a 30% reduction in tumour size were predicted and interpreted in the context of published minimally important differences. RESULTS: All patients with tumour evaluations and FACT-M data at baseline and week 7 (n=39), week 13 (n=27), week 19 (n=20) and week 25 (n=19) were analysed. One additional patient was included in EQ-5D analyses. Median SLD at baseline was 83mm (range: 16-404mm). Regression analyses showed associations between change in HRQoL outcomes and SLD at week 7. Specifically, a 30% SLD reduction at week 7 was associated with clinically meaningful improvements (mean change) in Functional Well-being (1.89), FACT-MTrial Outcome Index (4.20), FACT-G total (3.84), FACT-M total (5.52) and EQ-5D-5L utility index (0.06). Gain in EQ5D-5L utility index remained at week 13 (0.03) but no other associations were observed at subsequent timepoints. CONCLUSIONS: Reductions in tumour size after 7 weeks of avelumab treatment were associated with clinically meaningful improvements in functioning and HRQoL.