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

Abstract

Background: 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. Aim: We evaluated whether prior treatment with curative or locoregional therapies influences sorafenib-specific survival. Methods: 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 (n = 413; 79%). The primary endpoint was overall survival (OS) from sorafenib initiation with prognostic factors tested on uni- and multivariate analyses. Results: Median OS for the entire cohort was 9 months; the median sorafenib duration was 2.8 months, with discontinuation being secondary to progression (n = 454; 58%) or toxicity (n = 149; 19%). PT patients had significantly longer OS than TN patients (10.5 vs. 6.6 months; p < 0.001). Compared to TN patients, PT patients had a better Child-Pugh (CP) class (CP A: 57 vs. 47%; p < 0.001) and a lower BCLC stage (BCLC A-B, 40 vs. 30%; p = 0.007). PT status preserved an independent prognostic role (p = 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%; p < 0.001). Conclusion: 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.

Reason of Discontinuation After Transarterial Chemoembolization Influences Survival in Patients with Hepatocellular Carcinoma

“…These patients showed a trend toward better PPS when treated with subsequent liver-directed or systemic treatment compared with BSC only (13 vs 5 months). These results are in line with post hoc analyses of the landmark phase III sorafenib trials and a recent international observational study [ 27 – 29 ], showing a clear survival benefit in strictly selected patients treated with sorafenib after TACE compared with those receiving BSC only [ 29 ]. Although sorafenib is the guideline-recommended treatment strategy after TACE failure [ 1 ], the predominantly intrahepatic pattern of progression at UTP (75%) implies that most patients may be candidate for both liver-directed (radioembolization) and systemic treatments (sorafenib).…”

The concept of therapeutic hierarchy for patients with hepatocellular carcinoma: A multicenter cohort study

“…In clinical practice, in fact, a relevant time‐related migration of many HCC patients along different treatment strategies and tumour stages exist during their oncologic history . More importantly, both Vitale et al and Yen et al demonstrated an incremental benefit to overall survival from the sequential exposure to multiple lines of therapy, supporting the adoption of both, the therapeutic hierarchy and treatment stage migration strategies, in eligible patients.…”

Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Edition)

“…Therefore, close follow-up must be performed for all patients. In the case of tumor recurrences, repeat resection, local ablation, TACE, radiation therapy, or systemic treatment [61] can be used based on the characteristics of tumor recurrences. For patients at high risk for tumor recurrence, postoperative TACE has been shown to be somewhat effective because it helps detect and control residual minimal intrahepatic cancer [62] (evidence level 4).…”