Background

HCC is the most common kind of liver cancer, accounting for 85% of cases, and it is the fourth leading cause of cancer mortality worldwide. Most patients are diagnosed at the advanced stage, which is associated with poor prognosis, negatively impacting QoL of patients and their willingness to comply with therapies. Inclusion of QoL metrics in clinical trials (CTs) is of particular importance for diseases with poor prognosis as they assess the intervention effect on patients’ functional status, psychological and social functioning, and wellbeing. This study aimed at understanding trends in the use of QoL metrics across CTs in aHCC and their role in HTA assessment across key European countries.

Methods

A focused comprehensive literature search was conducted using PubMed and Clinicaltrials.gov. A screening for pertinent articles was performed by reviewing titles and abstracts related to first- (1L) and second-line (2L) treatments in aHCC Phase II and III trials. Study selection and data extraction were independently performed by two researchers, based on relevance to aHCC and QoL metrics.

Results

The literature search identified 173 records of which 22 met inclusion criteria: 8 (9%) published papers and 14 (17%) on-going CTs. The study identified 2 HCC-specific, 2 cancer-specific and 2 generic QoL instruments. EORTC-QLQ-C30 and EORTC-QLQ-HCC18 were assessed in all published CT studies in 1L (n=6), whereas FACT-Hep and EQ-5D were used in 2L CT studies (n=2). EORTC-QLQ-C30 and EORTC-QLQ-HCC18 are the most used metrics in ongoing CTs (n=11). QoL instruments are accepted by HTA if appropriately included in CTs study design and method of controlling alpha inflation risk is considered important.

Conclusion

Despite the high relevance of QoL metrics in diseases with poor prognosis, such as aHCC, this study highlighted the limited use of QoL endpoints in aHCC clinical trials, not always reflecting HTA requirements in EU.