A Systematic Literature Review of Patient-Reported Outcomes in Phase III Randomized Controlled Trials of Hepatocellular Carcinoma in a First-Line Setting

OBJECTIVES: Hepatocellular carcinoma (HCC) is a leading cause of death and is associated with significant morbidity. Patient-reported outcomes (PROs) provide insight into the patient's subjective experience with disease and treatment. This study evaluated the PROs among the advanced HCC patients treated with first-line systemic therapy.

METHODS: EMBASE^® and MEDLINE^® were searched for English language articles published from inception to December 2022 for randomized controlled trials (RCTs) evaluating PROs in advanced HCC. The risk of bias assessment was performed using Cochrane’s RoB-2 tool.

RESULTS: Four phase III, open-label RCTs were included (IMbrave150, REFLECT, CheckMate 459, and HIMALAYA). The HCC patients were recruited globally across multiple centers in all RCTs. Three general (EORTC-QLQ C30, EQ-VAS, EQ-5D index) and two disease-specific (EORTC QLQ-HCC18, FACT-Hep) instruments were utilized to evaluate PROs among advanced HCC patients. The interventions assessed were atezolizumab + bevacizumab, tremelimumab + durvalumab (STRIDE regimen), lenvatinib, nivolumab, durvalumab and sorafenib. Compared to sorafenib, atezolizumab + bevacizumab, STRIDE regimen, and lenvatinib reduced the risk of deterioration on EORTC QLQ-C30 generic cancer symptom scales such as fatigue, pain, diarrhea, appetite loss, nausea, and vomiting. Atezolizumab + bevacizumab also reduced the risk of deterioration on symptom scales (dyspnoea and insomnia) and functioning (emotional, social, and cognitive). Further, atezolizumab + bevacizumab, and lenvatinib reduced the risk of deterioration on disease-symptom scales (body image and nutrition) compared to sorafenib. Atezolizumab + bevacizumab was associated with a reduced risk of deterioration on the HCC18 disease-specific symptom scale (fatigue, pain, abdominal swelling). Compared with sorafenib, nivolumab was associated with a reduced risk of deterioration on all disease-specific functioning and symptom scales of FACT-Hep (total, physical well-being, functional well-being, and hepatobiliary cancer).

CONCLUSIONS: Treatment of advanced HCC requires consideration of HRQOL. First-line systematic therapies may delay functional decline in advanced hepatocellular carcinoma by improving HRQOL in clinically relevant domains compared with sorafenib.