Supplementary Material for: Treatment Stage Migration Maximizes Survival Outcomes in Patients with Hepatocellular Carcinoma Treated with Sorafenib: An Observational Study

<b><i>Background:</i></b> Level I evidence supports the use of sorafenib in patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma, where heterogeneity in efficacy exists due to varying clinicopathologic features of the disease. <b><i>Aim:</i></b> We evaluated whether prior treatment with curative or locoregional therapies influences sorafenib-specific survival. <b><i>Methods:</i></b> From a prospective data set of 785 consecutive patients from international specialist centres, 264 patients (34%) were treatment naïve (TN) and 521 (66%) were pre-treated (PT), most frequently with transarterial chemoembolization (<i>n</i> = 413; 79%). The primary endpoint was overall survival (OS) from sorafenib initiation with prognostic factors tested on uni- and multivariate analyses. <b><i>Results:</i></b> Median OS for the entire cohort was 9 months; the median sorafenib duration was 2.8 months, with discontinuation being secondary to progression (<i>n</i> = 454; 58%) or toxicity (<i>n</i> = 149; 19%). PT patients had significantly longer OS than TN patients (10.5 vs. 6.6 months; <i>p</i> &lt; 0.001). Compared to TN patients, PT patients had a better Child-Pugh (CP) class (CP A: 57 vs. 47%; <i>p</i> &lt; 0.001) and a lower BCLC stage (BCLC A-B, 40 vs. 30%; <i>p</i> = 0.007). PT status preserved an independent prognostic role (<i>p</i> = 0.002) following adjustment for BCLC stage, α-fetoprotein, CP class, aetiology, and post-sorafenib treatment status. PT patients were more likely to receive further anticancer treatment after sorafenib (31 vs. 9%; <i>p</i> &lt; 0.001). <b><i>Conclusion:</i></b> Patients receiving sorafenib after having failed curative or locoregional therapies survive longer and are more likely to receive further treatment after sorafenib. This suggests an incremental benefit to OS from sequential exposure to multiple lines of therapy, justifying treatment stage migration in eligible patients.