Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma

Abou‐Alfa, Ghassan K.; Meyer, Tim; Cheng, Ann Lii; El-Khoueiry, Anthony B.; Rimassa, Lorenza; Ryoo, Baek Yeol; Çiçin, İrfan; Merle, Philippe; Chen, Yen Hsun; Park, Joong-Won; Blanc, Jean Frédéric; Bolondi, Luigi; Klümpen, Heinz Josef; Chan, Stephen L.; Zagonel, Vittorina; Pressiani, Tiziana; Ryu, Min Hee; Venook, Alan P.; Hessel, Colin M.; Borgman-Hagey, Anne E.; Schwab, Gisela; Kelley, Robin Kate

doi:10.1056/nejmoa1717002

Cited by 1,888 publications

(1,924 citation statements)

References 30 publications

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“…For example, a recently published trial of rituximab plus lenalidomide versus rituximab plus chemotherapy reported in its abstract conclusion that “the safety profile differed in the two groups.”5 Although this statement is not very informative, it is at least an objective description and readers can look at the adverse effect profiles and frequencies for themselves. Another trial abstract concluded: “The rate of high-grade adverse events in the cabozantinib group was approximately twice that observed in the placebo group.”12…”

Section: Better Reportingmentioning

confidence: 99%

Reporting harms more transparently in trials of cancer drugs

Gyawali

Shimokata

Honda

et al. 2018

BMJ

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Section: Better Reportingmentioning

confidence: 99%

Reporting harms more transparently in trials of cancer drugs

Gyawali

Shimokata

Honda

et al. 2018

BMJ

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“…The median overall survival (OS) was substantially longer in CPA compared with CPB patients (9.5 months [95% CI, 8.5-14.8 months] vs 3.2 months [95% CI, 2.7-6.0 months]). [14][15][16] There are limited data to guide the dosing of these agents in patients with CPB or greater hepatic dysfunction. [7][8][9][10][11][12][13] No starting dose adjustment is indicated for CPB liver dysfunction in the drug label.…”

Section: Introductionmentioning

confidence: 99%

Nivolumab in patients with advanced hepatocellular carcinoma and Child‐Pugh class B cirrhosis: Safety and clinical outcomes in a retrospective case series

Kambhampati

Bauer

Bracci

et al. 2019

Cancer

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BACKGROUND: Nivolumab demonstrated durable responses and safety in patients with hepatocellular carcinoma (HCC) with Child-Pugh class A cirrhosis in the CheckMate 040 trial, with rates of hepatotoxicity that were similar to those of non-HCC populations. To the authors' knowledge, the safety and efficacy of nivolumab has not been established in patients with Child-Pugh class B (CPB) cirrhosis, a population with limited therapeutic options and a poor prognosis. METHODS: The authors conducted a retrospective case series of patients with advanced HCC and CPB cirrhosis who were treated with nivolumab and enrolled in the University of California at San Francisco Hepatobiliary Tissue Bank and Registry. Safety endpoints included rates of grade ≥3 adverse events (AEs) (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.03]) and serious AEs, immune-related AEs (irAE), steroid requirement, and discontinuation. Efficacy endpoints included time on treatment, the objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, overall survival, and progression-free survival. RESULTS: A total of 18 patients were included, with 72% of them (13 of 18 patients) previously treated with sorafenib. The majority of patients (94%; 17 of 18 patients) experienced a grade ≥3 AE, with treatment-related grade ≥3 AEs reported in 28% of patients (5 of 18 patients). irAEs were reported to occur in approximately 50% of patients (9 of 18 patients), and 28% (5 of 18 patients) required steroids. Treatment-related AEs required discontinuation in 4 patients (22%). The median time on treatment was 2.3 months (95% CI, 1.9 months to upper bound not estimable). The objective response rate was 17% (3 of 18 patients), including 2 partial responses and 1 complete response. The median overall survival from the time of nivolumab initiation was 5.9 months (95% CI, 3 months to upper bound not estimable), with a median progression-free survival of 1.6 months (95% CI, 1.4-3.5 months). CONCLUSIONS: Patients with CPB HCC experienced high rates of AEs, although the frequency of irAEs was similar to that of patients with Child-Pugh class A HCC in the CheckMate 040 trial. A subset of patients experienced prolonged tumor responses. Nivolumab warrants further study in patients with CPB HCC. Cancer 2019;125:3234-3241.

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“…4,5 Hepatitis B continues to drive the majority of the global burden of HCC, especially in southeast Asia and sub-Saharan Africa. After the development of sorafenib, 8,9 4 agents have demonstrated improved outcome data: lenvatinib 10 in the first-line and regorafenib, 11 cabozantinib, 12 and ramucirumab 13 after first-line disease progression. Despite those curative efforts, the majority of patients ultimately will experience a recurrence of their disease.…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint inhibitors for hepatocellular carcinoma

Dika

Khalil

Abou‐Alfa

2019

Cancer

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The position of immunotherapy as a pillar of systemic cancer treatment has been firmly established over the past decade. Immune checkpoint inhibitors are a welcome option for patients with different malignancies. This is in part because they offer the possibility of durable benefit, even for patients who have failed other treatment modalities. The recent demonstration that immunotherapy is effective for patients with hepatocellular carcinoma (HCC) is a milestone in the history of this recalcitrant disease. The treatment of HCC has been a challenge, and for many years was limited to the tyrosine kinase inhibitor sorafenib and to several novel tyrosine kinase inhibitors that have shown efficacy and have been approved. The current role of immune checkpoint inhibitors in the management of HCC, and how this role is likely to evolve in the years ahead, are key. Other than efforts evaluating single checkpoint inhibitors, potential combination strategies, including combinations with existing local and systemic approaches, including novel therapies are evolving. This is understandably of special interest considering the potential unique immune system of the liver, which may impact the use of immunotherapy in patients with HCC going forward, and how can it be enhanced further. Cancer 2019;125:3312-3319.

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Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma

Cited by 1,888 publications

References 30 publications

Reporting harms more transparently in trials of cancer drugs

Reporting harms more transparently in trials of cancer drugs

Nivolumab in patients with advanced hepatocellular carcinoma and Child‐Pugh class B cirrhosis: Safety and clinical outcomes in a retrospective case series

Immune checkpoint inhibitors for hepatocellular carcinoma

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