OBJECTIVES: Recent therapeutic developments in HCC are positioned to change the treatment landscape. Regorafenib received US approval for 2L aHCC, and early results for nivolumab in this setting indicate efficacy and manageable safety. Given the symptom burden associated with HCC, understanding the comparative safety and related cost is vital when evaluating treatments. In the absence of a head-to-head trial, MAIC was performed to compare the treatments with respect to high-grade TRAEs and associated costs.

METHODS: Frequency, grade, and attribution of TRAEs were extracted from patient-level data collected in the sorafenib experienced dose expansion cohort of CheckMate 040, a Phase 1/2 non-comparative study. MAIC was performed to adjust baseline characterisitics between the nivolumab (n=145) and the regorafenib RESORCE trial (n=374). Subsequently, odds ratios (OR) comparing nivolumab with regorafenib for grade 3-4 TRAEs and any TRAE were calculated. TRAE costs were estimated from associated principle ICD-9 diagnosis codes from the 2012-2014 Healthcare Cost and Utilization Project National Inpatient Sample data. Per Common Terminology Criteria for Adverse Events guidelines, all grade 3-4 AEs were assumed to require inpatient hospitalization.

RESULTS: Based on the MAIC, 10 grade 3-4 TRAEs were attributed to nivolumab compared to 243 with regorafenib. Grade 3-4 TRAEs and any grade TRAEs leading to discontinuation were significantly less frequent in nivolumab vs regorafenib (OR: 0.23 (95% CI: 0.14-0.39) and OR: 0.25 (0.08-0.83), respectively). No significant between-treatment differences were observed for specific grade 3-4 TRAEs though point estimates tended to favour nivolumab. The per-patient costs of managing grade 3-4 TRAEs were 10.2 times higher for regorafenib compared to nivolumab ($3,946 vs $385).

CONCLUSIONS: Nivolumab was associated with reduced odds of grade 3-4 TRAEs and discontinuation due to TRAEs. This translates into reduced inpatient expenditures associated with the management of patients on nivolumab compared with regorafenib.