Prognostic factors and disease course in patients enrolled onto clinical trials of second-line therapy for hepatocellular carcinoma

406 Background: Prognostic factors of survival and disease course in patients with hepatocellular carcinoma (HCC) and preserved liver reserves, enrolled onto clinical trials of second-line treatments after sorafenib, are unclear. Methods: This single-center database analysis included all patients with Child-Pugh A score and ECOG performance status (PS) 0 - 1 participating between 2012 and 2017 in clinical trials of second-line systemic treatments for advanced HCC. Patients received first-line sorafenib and experienced either disease progression (PD) to sorafenib or were sorafenib-intolerant. Their clinicopathologic characteristics were correlated with overall survival (OS, calculated from the first day of second-line treatment to death or last visit available), and post-treatment survival (PTS, calculated from the date of end-of-treatment to death or last follow-up). Results: Ninety-nine patients (21 sorafenib-intolerant, 78 progressors) were enrolled onto trials of checkpoint inhibitors (CPI, 23 patients), tyrosine kinase inhibitors (TKI, 44 patients) versus best supportive care (BSC, 24 patients), open-label TKI (8 patients). Overall, median OS was 9.4 months (9.6, 9.8, and 8.0 months for CPI, TKI and BSC, respectively; p = 0.493). Median time-to-treatment failure was 3.5, 4.4, 3.7 months for CPI, TKI and BSC, respectively (p = 0.561). In multivariable analyses, worse OS was linked to high neutrophil/lymphocyte ratio (Hazard Ratio, HR = 1.13; p = 0.005) and macrovascular invasion [(MVI), HR = 2.59; p < 0.001]. Second-line treatment discontinuation due to liver failure independently conferred worse PTS than adverse events (HR = 2.32; p = 0.111) or PD (HR = 3.44; p = 0.002), as did ECOG PS > 1 at EOT (HR = 3.05; p = 0.002). Death rate within 30 days of end-of-treatment was 4.2% on placebo versus 10.5% on IO versus 22.9% on TKI. Conclusions: In this homogeneous cohort of compensated HCC patients pre-treated with sorafenib, MVI and NLR at start of second-line clinical trial are prognostic factors of OS. Besides ECOG PS and liver failure, further predictors of subsequent PTS to inform treatment options beyond second-line were not identified.