Second‐line treatment of hepatocellular carcinoma after sorafenib: Characterizing treatments used over the past 10 years and real‐world eligibility for cabozantinib, regorafenib, and ramucirumab

Fung, A.; Tam, Vincent C.; Meyers, Daniel E.; Sim, Hao‐Wen; Knox, Jennifer J.; Zaborska, Valeriya O.; Ko, Yoo‐Joung; Batuyong, Eugene; Samawi, Haider; Cheung, Winson Y.; Lee‐Ying, Richard M.

doi:10.1002/cam4.3116

Cited by 19 publications

(24 citation statements)

References 16 publications

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“…For instance, Fung et al [24] reported that only 13.1% of 720 sorafenib-experienced patients were eligible for cabozantinib, regorafenib, or ramucirumab as a second-line treatment if strict eligibility criteria were used. If the eligibility criteria were extended to also include patients with ECOG-PS 2 or Child-Pugh class B7, then the eligibility rate increased to 31%, but with a lesser survival expectancy [24]. The proportion of patients theoretically eligible for a third-line treatment has never explicitly been investigated, but the proportion is expected to be even lower than that reported for the second-line setting.…”

Section: Discussionmentioning

confidence: 99%

Real-Life Clinical Data of Cabozantinib for Unresectable Hepatocellular Carcinoma

et al. 2021

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Introduction: Cabozantinib has been approved by the European Medicine Agency (EMA) for hepatocellular carcinoma (HCC) previously treated with sorafenib. Cabozantinib is also being tested in combination with immune checkpoint inhibitors in the frontline setting. Real-life clinical data of cabozantinib for HCC are still lacking. Moreover, the prognostic factors for HCC treated with cabozantinib have not been investigated. Methods: We evaluated clinical data and outcome of HCC patients who received cabozantinib in the legal context of named patient use in Italy. Results: Ninety-six patients from 15 centres received cabozantinib. All patients had preserved liver function (Child-Pugh A), mostly with an advanced HCC (77.1%) in a third-line setting (75.0%). The prevalence of performance status (PS) > 0, macrovascular invasion (MVI), extrahepatic spread, and alpha-fetoprotein (AFP) >400 ng/mL was 50.0, 30.2, 67.7, and 44.8%, respectively. Median overall survival (OS) and progression-free survival were 12.1 (95% confidence interval 9.4–14.8) and 5.1 (3.3–6.9) months, respectively. Most common treatment-related adverse events (AEs) were fatigue (67.7%), diarrhoea (54.2%), anorexia (45.8%), HFSR (43.8%), weight loss (24.0%), and hypertension (24.0%). Most common treatment-related Grade 3–4 AEs were fatigue (6.3%), HFSR (6.3%), and increased aminotransferases (6.3%). MVI, ECOG-PS > 0, and AFP >400 ng/mL predicted a worse OS. Discontinuation for intolerance and no new extrahepatic lesions at the progression were associated with better outcomes. Conclusions: In a real-life Western scenario (mostly in a third-line setting), cabozantinib efficacy and safety data were comparable with those reported in its registration trial. Data regarding the prognostic factors might help in patient selection and design of clinical trials.

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Section: Discussionmentioning

confidence: 99%

Real-Life Clinical Data of Cabozantinib for Unresectable Hepatocellular Carcinoma

et al. 2021

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“…It also determined the rate of patients eligible for new therapies if strict eligibility criteria (SEC; as defined in the respective studies) were used, compared with more liberal modified eligibility criteria (MEC, including Child–Pugh-B7 and ECOG 2). 61 …”

Section: Regorafenib Treatment In Real-life Clinical Practicementioning

confidence: 99%

Experience with regorafenib in the treatment of hepatocellular carcinoma

Granito

Forgione

Marinelli

et al. 2021

Therap Adv Gastroenterol

105

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Regorafenib is a diphenylurea oral multikinase inhibitor, structurally comparable to sorafenib, which targets a variety of kinases implicated in angiogenic and tumor growth-promoting pathways. Regorafenib was the first agent to positively show significant survival advantage as a second-line therapy in patients with unresectable hepatocellular carcinoma (HCC) who had previously failed first-line treatment with sorafenib. Recent evidence has shown that its antitumor efficacy is due to a comprehensive spectrum of tumor neo-angiogenesis and proliferation inhibition and immunomodulatory effects on the tumor microenvironment, which plays a crucial role in tumor development. This review addresses the rationale and supporting evidence for regorafenib’s efficacy in HCC that led to regorafenib’s approval as a second-line therapy. In addition, we review proof from clinical practice studies that validate the RESORCE trial results. We discuss regorafenib’s potential role in the newly emerging therapeutic strategy based on combination with immune checkpoint blockade and its possible extensibility to patient categories not enrolled in the registrative study.

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“…A Canadian study characterized subsequent therapies received by HCC patients following sorafenib and determined the rate of patients eligible for novel therapies if strict eligibility criteria (SEC) (as defined in their respective trials) were used, compared to more liberal modified eligibility criteria (MEC, including Child-Pugh B7 and ECOG 2). 58 A total of 730 patients were identified with 172 (23.6%) receiving subsequent treatment (regorafenib, cabozantinib or ramucirumab). Patients receiving subsequent treatment had longer overall survival than patients who did not (12.1 versus 3.3 months; p<0.001).…”

Section: Dovepressmentioning

confidence: 99%

Section: Real-life Clinical Practice Of Regorafenib Treatment In Hccmentioning

confidence: 99%

Regorafenib Combined with Other Systemic Therapies: Exploring Promising Therapeutic Combinations in HCC

Granito¹,

Marinelli²,

Forgione³

et al. 2021

JHC

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Regorafenib was the first drug to demonstrate a survival benefit as a second-line agent after sorafenib failure in patients with unresectable hepatocellular carcinoma (HCC). Recent studies have shown that its mechanism of action is not only limited to its very broad spectrum of inhibition of angiogenesis, tumor proliferation, spread, and metastasis, but also to its immunomodulatory properties that have favorable effects on the very intricate role that the tumor microenvironment plays in carcinogenesis and tumor growth. In this review, we discuss rationale and evidence supporting regorafenib efficacy in HCC and that led to its approval as a second-line treatment, after sorafenib failure. We also discuss the evidence from clinical practice studies that confirm the results previously achieved in clinical trials. Finally, we analyze the potential role of regorafenib in emerging combined treatment approach with immunotherapy strategies using immune checkpoint blockade and its potential extension to patient categories not included in the registrative study.

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Second‐line treatment of hepatocellular carcinoma after sorafenib: Characterizing treatments used over the past 10 years and real‐world eligibility for cabozantinib, regorafenib, and ramucirumab

Cited by 19 publications

References 16 publications

Real-Life Clinical Data of Cabozantinib for Unresectable Hepatocellular Carcinoma

Real-Life Clinical Data of Cabozantinib for Unresectable Hepatocellular Carcinoma

Experience with regorafenib in the treatment of hepatocellular carcinoma

Regorafenib Combined with Other Systemic Therapies: Exploring Promising Therapeutic Combinations in HCC

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