Phase III trial of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC).

Căinap, Călin; Qin, Shukui; Huang, Wen-Tsung; Chung, Ik‐Joo; Pan, Hongming; Cheng, Ying; Kudo, Masatoshi; Kang, Yoon‐Koo; Chen, Pei‐Jer; Toh, Han Chong; Gorbunova, Vera; Eskens, Ferry A.L.M.; Qian, Jiang; McKee, Mark D.; Ricker, Justin L.; Carlson, Dawn M.; Nowiem, Saied El

doi:10.1200/jco.2013.31.4_suppl.249

Cited by 60 publications

(51 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is reflected in the lack of agents that were approved before sorafenib and in the failure of recent clinical trials of other systemic therapies to meet their primary end points [4,[16][17][18][19]. As sorafenib is currently the only approved systemic therapy that is available for HCC, it is important for physicians to know how best to use this agent in clinical practice in order to maximize the therapeutic benefits for their patients.…”

mentioning

confidence: 99%

Refining Sorafenib Therapy: Lessons from Clinical Practice

et al. 2014

View full text Add to dashboard Cite

AbstrAct:Understanding the best use of sorafenib is essential in order to maximize clinical benefit in hepatocellular carcinoma. Based on Phase III and noninterventional study data, as well as our extensive experience, we discuss dose modification in order to manage adverse events, disease response evaluation and how to maximize treatment benefit. Sorafenib should be initiated at the approved dose (400 mg twice daily) and reduced/ interrupted as appropriate in order to manage adverse events. Dose modification should be considered before discontinuation. Appropriate tumor response assessment is critical. Focusing on radiologic response may result in premature sorafenib discontinuation; symptomatic progression should also be considered. If second-line therapies or trials are unavailable, continuing sorafenib beyond radiologic progression may provide a clinical benefit. Our recommendations enable the maximization of treatment duration, and hence clinical benefit, for patients. Keywords:• adverse event managementIt is well established that hepatocellular carcinoma (HCC) is a complex and heterogeneous disease that is affected by multiple genetic and epigenetic alterations [1]. In the overwhelming majority of patients, liver cirrhosis -another complex disease in its own right -is superimposed on HCC. As a result, the prognostic range for these patients varies considerably and continues to change for each patient at every time point over the clinical course of their disease. A meta-analysis of 30 clinical trials into which HCC patients were enrolled for palliative treatment reflects this heterogeneity. It demonstrated a high variability in survival among untreated patients and concluded that no single patient characteristic alone could predict outcome [2].The prognosis and treatment options for HCC are generally related to tumor stage and liver function at presentation [3,4]. In the west, approximately 30% of all patients with HCC are diagnosed in

show abstract

mentioning

confidence: 99%

Refining Sorafenib Therapy: Lessons from Clinical Practice

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Many molecular agents have been studied, but the only one that showed efficacy in terms of overall survival and time to progression has been sorafenib, as was revealed by two phase III, randomized-controlled studies (91,92). Those results have been prospectively confirmed in different clinical trials in which sorafenib was the control arm (93)(94)(95)(96)(97) as well as in multiple prospective studies in real life clinical practice (98-100). Furthermore, sorafenib is able to maintain its efficacy despite the etiology of liver disease, the baseline status of neoplasm, the presence or absence of cancer related symptoms or previous therapies (101).…”

Section: Improvements In the Treatment Of Intermediate-advanced Hccmentioning

confidence: 55%

New challenges in clinical research on hepatocellular carcinoma

Díaz-González¹,

Forner²,

C³

et al. 2015

Rev Esp Enferm Dig

View full text Add to dashboard Cite

This is an updated review of screening, early diagnosis and treatment of hepatocellular carcinoma, focusing on the advancements occurred in the last years and highlighting the challenges in clinical research.Hepatocellular carcinoma (HCC) is nowadays the sixth most frequent cancer worldwide with up to 740,000 new cases diagnosed each year, and it is the third most prevalent cause of cancer-relateddeath worldwide (1). This neoplasm usually appears linked to an underlying liver disease, being one of the most relevant causes of death in patients diagnosed of liver cirrhosis (2,3). In the last years, important advancements in terms of diagnosis, staging and treatment of HCC, improving the management and outcome of the disease, have been made (4-7). Despite the fact that these improvements have absolutely changed natural history of HCC, there are several areas that still need further advancements.The aim of this document is to discuss some controversial aspects, which in our opinion constitute real challenges in clinical research of HCC.Key words: Hepatocellular carcinoma. Hepatic oncology. Sorafenib. Transarterial chemoembolization. AFP. IMPROVING EARLY DIAGNOSISFrom the basis that the only possibility to offer and apply treatments with curative intention is being able to diagnose HCC at early stages, when there are not cancer related symptoms. Since this option is only feasible if screening is performed in population at risk, scientific guidelines recommend performing abdominal ultrasonography (US) in every patient with liver cirrhosis. Despite the recommendation of HCC screening by the Spanish guidelines (4), one registry study performed in Spain which included 62 centers and 705 patients diagnosed of HCC within a period of time of 4 months showed that just 47% of HCC patients were diagnosed in the setting of surveillance and less than a half were diagnosed at early stage (8).This data shows that early diagnosis, a key issue to be able to significantly reduce HCC-related mortality, is one of the most relevant issues that deserve further efforts from scientific community. Aiming to evaluate which were the causes of screening program fail in the United States of America, Singal et al. evaluated 1,005 patients included in the HALT-C prospective study. A third part of patients did not adhere to an adequate screening program and, in 70% of cases that were diagnosed at an advanced stage, the main reason was the absence of detection in US (9).With the aim of improving detection rate, it is crucial to establish formative programs in order to certify the capability of being able to carry on this activity and it is necessary to use up-to-date ultrasonography scans in order to perform an optimal liver exploration. Tumor markers could be a useful tool to overcome theoretical limitations of US: its evaluation is not subjective, does not depend on the operator and it may be reproducible, as well as it is relatively cheap and a tool easy to access in areas with low monetary income. Regrettably, different tumor markers ev...

show abstract

“…Sorafenib vs sorafenib + erlotinib 358 vs 362 Sorafenib: 8.5 Sorafenib + erlotinib: 9.5 Cheng et al [105] (SUN1170 trial) Sorafenib vs sunitinib 544 vs 530 Sorafenib: 10.2 Sunitinib: 7.9 Cainap et al [106] (LIGHT trial) Sorafenib vs linifanib 517 vs 518 Sorafenib: 9.8 Linifanib: 9.1 Johnson et al [107] (BRISK-FL trial)…”

Section: Patients N Overall Survival Mounclassified

“…The antiangiogenic tyrosine kinase inhibitors, sunitinib [105] , linifanib [106] , brivanib [107,108] , or the combination of sorafenib with erlotinib [109] are not superior to sorafenib in sorafenib-naïve advanced HCC patients, or as a second-line therapy [110] (Table 1). This may be due to the fact that inhibition of a single signaling pathway can induce feedback activation of other pathways.…”

Section: Other Molecular Targeted Agentsmentioning

confidence: 99%

Recent advances in multidisciplinary management of hepatocellular carcinoma

Gomaa¹

2015

WJH

View full text Add to dashboard Cite

Phase III trial of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC).

Cited by 60 publications

References 0 publications

Refining Sorafenib Therapy: Lessons from Clinical Practice

Refining Sorafenib Therapy: Lessons from Clinical Practice

New challenges in clinical research on hepatocellular carcinoma

Recent advances in multidisciplinary management of hepatocellular carcinoma

Contact Info

Product

Resources

About