Predictors of survival in patients with advanced hepatocellular carcinoma who permanently discontinued sorafenib

Abstract

Treatment with sorafenib of patients with advanced hepatocellular carcinoma is challenged by anticipated discontinuation due to tumor progression, liver decompensation, or adverse effects. While postprogression survival is clearly determined by the pattern of tumor progression, understanding the factors that drive prognosis in patients who discontinued sorafenib for any reason may help to improve patient management and second-line trial design. Patients consecutively admitted to three referral centers who were receiving best supportive care following permanent discontinuation of sorafenib for any reason were included. Postsorafenib survival (PSS) was calculated from the last day of treatment to death or last visit available. Two hundred and sixty patients were included in this prospective study, aged 67 years, 60% with hepatitis C, 51% Child-Pugh A, 83% performance status (PS) 1, 41% with macroscopic vascular invasion, and 38% with extrahepatic tumor spread. Overall, median PSS was 4.1 (3.3-4.9) months, resulting from 4.6 (3.3-5.7) months for 123 progressors, 7.3 (6.0-10.0) months in 77 with adverse effects, and 1.8 (1.6-2.4) months in 60 decompensated patients (P < 0.001). Postsorafenib survival was independently predicted by PS, prothrombin time, extrahepatic tumor spread, macrovascular invasion, and reason for discontinuation. Two hundred patients potentially eligible for second-line therapy had a PSS of 5.3 (4.6-7.1) months, which was dependent on reasons of discontinuation (P 5 0.004), PS (P < 0.001), macrovascular invasion (P < 0.001), and extrahepatic metastases (P < 0.002). Conclusion: Discontinuation due to adverse effects in the absence of macrovascular invasion, extrahepatic metastases, and deteriorated PS predicts the best PSS in compensated patients, thereby setting the stage for both improved patient counseling and selection for second-line therapy. (HEPATOLOGY 2015;62:784-791)

Postsorafenib systemic treatments for hepatocellular carcinoma: questions and opportunities after the regorafenib trial

“…This is a particularly critical process since HCC has a strongly heterogeneous natural history and biology [50]. Information about this topic are found in two brilliant papers by Reig et al [51] and Iavarone et al [52]. Reig et al [51] prospectively followed 147 HCC patients treated with sorafenib, assessing their radiological progression at week 4 and then every 8 weeks using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.…”

“…Iavarone and colleagues [52] analyzed the predictors of OS in patients who permanently discontinued sorafenib. Analyzing 200 patients potentially eligible for second-line therapy, postsorafenib survival was dependent on reasons of discontinuation (intolerance, progressive disease, liver function deterioration), performance status, macrovascular invasion and extrahepatic spread.…”

Report from European Association for the Study of the Liver: HCC Summit, Geneva, Switzerland, 2–5 February 2017

“…While waiting for these trials and regorafenib approval in all countries, there is consensus on continuing sorafenib in patients with radiological progressive but clinically stable disease also because sorafenib interruption could result in a rapid and symptomatic disease progression [23].…”

New challenges in clinical research on hepatocellular carcinoma

“…Accordingly, there are several trials aimed to identify potential polymorphisms in genes associated with angiogenic response (VEGFA, ANGPT2 and PLA-2G12A) that could allow us to recognize different patient's profiles in order to adjust treatment (111)(112)(113). Finally, in those patients with an HCC in intermediate/ advanced stage treated with sorafenib, the type of radiological progression has been identified as a statistically significant independent predictor of the post-progression survival (100,114). In that regard, the development of a new extrahepatic lesion or vascular invasion is the type of progression associated with the poorest prognosis.…”

“…In the trial design and target population selection, it is mandatory to register those events appeared during sorafenib therapy. As discussed above, the pattern of radiological progression has a statistically significant impact on post-progression survival (100,114). In addition, second-line trials recruit patients who, despite sorafenib failure, have a preserved liver function and good general condition (ECOG-PS 0-1), and in many cases had presented adverse events linked to good prognosis (110).…”