Second-line treatment with nivolumab, cabozantinib, regorafenib, or best supportive care in patients with advanced hepatocellular carcinoma: analysis at a Hispanic-majority NCI-designated cancer center

Background: In the last four years, six regimens were approved by the Food and Drug Association as second-line therapies for advanced hepatocellular carcinoma (HCC). However, there are significant differences between real-world and clinical trial populations. We analyzed survival and toxicities among second-line therapies for HCC in our population. Methods: We performed a retrospective cohort study of patients with advanced HCC who received second-line therapies (tyrosine kinase inhibitor or TKI; immunotherapy or IO) or best supportive care (BSC) at a tertiary-referral cancer center serving the South Texas region. Progression-free survival (PFS) was determined, and adverse events were compared between therapies. Results: In our cohort, median age was 60 years (n=65), and 49 (75%) were Hispanic. 58 (89%) patients received second-line therapy. Child-Pugh (CP) score of cohort: A, 18%; B, 55%; C, 26%. Median PFS (mPFS) was 3.1 months with TKI (n=6), 3.3 months with IO (n=27), and 1.3 months with BSC (n=25). There was improved survival with IO compared to BSC [hazards ratio (HR) =0.31; 95% confidence interval (CI): 0.15–0.63; P=0.0014]. There was no significant difference comparing IO to TKI (HR =0.94; 95% CI: 0.31–2.86; P=0.92), but a trend to improved PFS with TKI when compared to BSC (HR =0.33; 95% CI: 0.10–1.04; P=0.058). TKI group had significantly more rash (P=0.01) and hand-foot syndrome (P<0.001) compared to IO and BSC. Conclusions: Our Hispanic-majority cohort with varying liver dysfunction, including CP-B & C cirrhosis, were more likely to receive IO or BSC. Both second-line treatment groups, IO or TKI, demonstrated increased mPFS compared to BSC and were tolerable compared to BSC, with expected toxicity per class of drug.