In the treatment of hepatocellular carcinoma (HCC), immune checkpoint inhibitor (ICI) based therapy has recently emerged. Clinical trials provided the basis for approval, but their limited applicability to real-world practice resulted from their stringent eligibility requirements. In addition, there is still no accepted norm for post-ICI treatment. This retrospective investigation comprised patients (pts) with advanced HCC who were treated with ICI as a single agent (ICI-SA) or in combination (ICI-C) across lines of therapy. The cohort consisted of 118 pts: median age 63 years (24, 88); 84% male; 35% Hispanic/Latino, 26% Asian, 19% Non-Hispanic White, 5% Black, and 15% unknown.
Etiology of cirrhosis: 13% Hepatitis B, 45% Hepatitis C, 16 % alcohol liver disease, 10% NAFLD and 16 % mixed/other; 73% had baseline Child Pugh (CP) A, 25% had CP-B, and 2% had CP-C; ALBI Scores were ≤ -2.60 in 32%, 2.60 and ≤-1.39 in 48%, and ≥-1.39 in 19% pts; 62% had extrahepatic disease and/or portal invasion; AFP was ≥ 400 ng/mL in 25% of pts. 81% of pts had prior local therapy. First-line systemic therapies were: TKIs in 52 pts (44%), ICI-SA in 42 (36%), ICI-C in 15 (13%), clinical trial agent (CTA) in 8 (7%), and chemotherapy in 1 (1%), with a median duration (dur) of 4 months (95% CI 2.3 to 4). Around 91 (77%) and 61 pts (52%) received ≥ 2 or 3 lines of therapy, respectively. About 57 pts had ICI-SA and 14 ICI-C in second line or beyond. Median dur of ICI therapy was 4 months (95% CI 3-5) for all lines. Post-ICI therapies included 11% ICI, 30% CTA and 59% TKIs. TKIs included sorafenib (46%), cabozantinib (27%), lenvatinib (15%), and regorafenib (27%). For the 118 pt cohort, mOS was 14 months (95% CI 12-19). For pts treated with ICI in first line, mOS was 11 months (0, 74); post-ICI mOS was 6 months (95% CI 3-9) and mPFS was 3 months (95% CI 2-3).
About 31 pts received a TKI post ICI; mOS for this subset was 19 months (15, 22); mOS from start of TKI post ICI was 6.5 months (4, 12). On multivariable regression analysis, ALBI score was associated with OS (HR 1.63, P=0.02, CI: 1.08-2.27). Patients with CP-A or B cirrhosis and advanced HCC may benefit from sequential systemic therapy that includes ICI. Patients with more severely impaired liver function and less stringent pt selection compared to clinical trials affected survival outcomes in this cohort. Using TKIs after ICI is doable, and there is some evidence of clinical activity, but more research is needed in this area.
Source – ASCO GI 2023
