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Erschienen in: Targeted Oncology 1/2019

14.02.2019 | Adis Drug Evaluation

Cabozantinib: A Review in Advanced Hepatocellular Carcinoma

verfasst von: Emma D. Deeks

Erschienen in: Targeted Oncology | Ausgabe 1/2019

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Abstract

Cabozantinib is an inhibitor of multiple receptor tyrosine kinases (RTKs) with roles in cancer pathogenesis. This review focuses on data relevant to the use of cabozantinib tablets (Cabometyx®) in the treatment of hepatocellular carcinoma (HCC) in patients who have been previously treated with the multi-RTK inhibitor sorafenib, an indication for which cabozantinib tablets are approved in the EU and USA. Approval of cabozantinib in this setting was based largely on the findings of CELESTIAL, a phase 3 trial in adults with advanced HCC who had previously received sorafenib, had progressive disease after at least one systemic therapy and had received up to two systemic treatments for their advanced disease. Compared with placebo in this study, cabozantinib prolonged both overall survival and progression-free survival, with these findings largely unaffected by patient/disease characteristics. The tolerability profile of cabozantinib in CELESTIAL was acceptable and consistent with that of other multi-RTK inhibitors, with adverse events that were manageable with dose modification and supportive care. Thus, cabozantinib is a welcome additional treatment option for use in adults with HCC previously treated with sorafenib.
Literatur
1.
Zurück zum Zitat Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRef Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRef
3.
Zurück zum Zitat Vogel A, Cervantes A, Chau I, et al. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018; 29(Suppl 4):iv238–55.CrossRefPubMed Vogel A, Cervantes A, Chau I, et al. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018; 29(Suppl 4):iv238–55.CrossRefPubMed
5.
6.
Zurück zum Zitat European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182–236.CrossRef European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182–236.CrossRef
7.
Zurück zum Zitat Raoul JL, Kudo M, Finn RS, et al. Systemic therapy for intermediate and advanced hepatocellular carcinoma: sorafenib and beyond. Cancer Treat Rev. 2018;68:16–24.CrossRefPubMed Raoul JL, Kudo M, Finn RS, et al. Systemic therapy for intermediate and advanced hepatocellular carcinoma: sorafenib and beyond. Cancer Treat Rev. 2018;68:16–24.CrossRefPubMed
10.
Zurück zum Zitat Yakes FM, Chen J, Tan J, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011;10(12):2298–308.CrossRefPubMed Yakes FM, Chen J, Tan J, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011;10(12):2298–308.CrossRefPubMed
11.
Zurück zum Zitat Xiang Q, Chen W, Ren M, et al. Cabozantinib suppresses tumor growth and metastasis in hepatocellular carcinoma by a dual blockade of VEGFR2 and MET. Clin Cancer Res. 2014;20(11):2959–70.CrossRefPubMed Xiang Q, Chen W, Ren M, et al. Cabozantinib suppresses tumor growth and metastasis in hepatocellular carcinoma by a dual blockade of VEGFR2 and MET. Clin Cancer Res. 2014;20(11):2959–70.CrossRefPubMed
12.
Zurück zum Zitat Nguyen L, Benrimoh N, Xie Y, et al. Pharmacokinetics of cabozantinib tablet and capsule formulations in healthy adults. Anticancer Drugs. 2016;27(7):669–78.CrossRefPubMed Nguyen L, Benrimoh N, Xie Y, et al. Pharmacokinetics of cabozantinib tablet and capsule formulations in healthy adults. Anticancer Drugs. 2016;27(7):669–78.CrossRefPubMed
13.
Zurück zum Zitat Nguyen L, Holland J, Mamelok R, et al. Evaluation of the effect of food and gastric pH on the single-dose pharmacokinetics of cabozantinib in healthy adult subjects. J Clin Pharmacol. 2015;55(11):1293–302.CrossRefPubMed Nguyen L, Holland J, Mamelok R, et al. Evaluation of the effect of food and gastric pH on the single-dose pharmacokinetics of cabozantinib in healthy adult subjects. J Clin Pharmacol. 2015;55(11):1293–302.CrossRefPubMed
14.
Zurück zum Zitat Nguyen L, Holland J, Ramies DA, et al. Effect of renal and hepatic impairment on the pharmacokinetics of cabozantinib. J Clin Pharmacol. 2016;56(9):1130–40.CrossRefPubMed Nguyen L, Holland J, Ramies DA, et al. Effect of renal and hepatic impairment on the pharmacokinetics of cabozantinib. J Clin Pharmacol. 2016;56(9):1130–40.CrossRefPubMed
15.
Zurück zum Zitat Nguyen L, Holland J, Miles D, et al. Pharmacokinetic (PK) drug interaction studies of cabozantinib: effect of CYP3A inducer rifampin and inhibitor ketoconazole on cabozantinib plasma PK and effect of cabozantinib on CYP2C8 probe substrate rosiglitazone plasma PK. J Clin Pharmacol. 2015;55(9):1012–23.CrossRefPubMed Nguyen L, Holland J, Miles D, et al. Pharmacokinetic (PK) drug interaction studies of cabozantinib: effect of CYP3A inducer rifampin and inhibitor ketoconazole on cabozantinib plasma PK and effect of cabozantinib on CYP2C8 probe substrate rosiglitazone plasma PK. J Clin Pharmacol. 2015;55(9):1012–23.CrossRefPubMed
16.
Zurück zum Zitat Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54–63.CrossRefPubMed Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54–63.CrossRefPubMed
17.
Zurück zum Zitat Schoffski P, Gordon M, Smith DC, et al. Phase II randomised discontinuation trial of cabozantinib in patients with advanced solid tumours. Eur J Cancer. 2017;86:296–304.CrossRefPubMed Schoffski P, Gordon M, Smith DC, et al. Phase II randomised discontinuation trial of cabozantinib in patients with advanced solid tumours. Eur J Cancer. 2017;86:296–304.CrossRefPubMed
18.
Zurück zum Zitat Kelley RK, Verslype C, Cohn AL, et al. Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled randomized discontinuation study. Ann Oncol. 2017;28(3):528–34.CrossRefPubMedPubMedCentral Kelley RK, Verslype C, Cohn AL, et al. Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled randomized discontinuation study. Ann Oncol. 2017;28(3):528–34.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Merle P, Rimassa L, Ryoo B, et al. Assessment of tumor response, AFP response, and time to progression in the phase 3 CELESTIAL trial of cabozantinib versus placebo in advanced hepatocellular carcinoma (HCC) [abstract no. O-011]. Ann Oncol. 2018;29(Suppl 5). Merle P, Rimassa L, Ryoo B, et al. Assessment of tumor response, AFP response, and time to progression in the phase 3 CELESTIAL trial of cabozantinib versus placebo in advanced hepatocellular carcinoma (HCC) [abstract no. O-011]. Ann Oncol. 2018;29(Suppl 5).
20.
Zurück zum Zitat Meyer T, Baron A, Gordan J, et al. Outcomes in patients (pts) with hepatitis B virus (HBV) in the phase 3 CELESTIAL trial of cabozantinib (C) versus placebo (P) in advanced hepatocellular carcinoma (HCC). [abstract no. 0-012]. In: International Liver Cancer Association Annual Meeting. 2018. Meyer T, Baron A, Gordan J, et al. Outcomes in patients (pts) with hepatitis B virus (HBV) in the phase 3 CELESTIAL trial of cabozantinib (C) versus placebo (P) in advanced hepatocellular carcinoma (HCC). [abstract no. 0-012]. In: International Liver Cancer Association Annual Meeting. 2018.
21.
Zurück zum Zitat Blanc JF, Meyer T, Cheng AL, et al. Assessment of disease burden in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in advanced hepatocellular carcinoma (HCC) [abstract no. 703P plus poster]. Ann Oncol. 2018;29(Suppl 8). Blanc JF, Meyer T, Cheng AL, et al. Assessment of disease burden in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in advanced hepatocellular carcinoma (HCC) [abstract no. 703P plus poster]. Ann Oncol. 2018;29(Suppl 8).
22.
Zurück zum Zitat Rimassa L, Cicin I, Blanc JF, et al. Outcomes based on age in the phase 3 CELESTIAL trial of cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC) [abstract no. 4090]. J Clin Oncol. 2018;36(Suppl). Rimassa L, Cicin I, Blanc JF, et al. Outcomes based on age in the phase 3 CELESTIAL trial of cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC) [abstract no. 4090]. J Clin Oncol. 2018;36(Suppl).
23.
Zurück zum Zitat Kelley R, El-Khoueiry A, Meyer T, et al. Outcomes by baseline alpha-fetoprotein (AFP) levels in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in previously treated advanced hepatocellular carcinoma (HCC). [abstract no. 702P plus poster]. Ann Oncol. 2018;29(Suppl 8). Kelley R, El-Khoueiry A, Meyer T, et al. Outcomes by baseline alpha-fetoprotein (AFP) levels in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in previously treated advanced hepatocellular carcinoma (HCC). [abstract no. 702P plus poster]. Ann Oncol. 2018;29(Suppl 8).
24.
Zurück zum Zitat Yau T, Cheng AL, Meyer T, et al. Outcomes by prior transarterial chemoembolization (TACE) in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC) [abstract no. 704P plus poster]. Ann Oncol. 2018;29(Suppl 8). Yau T, Cheng AL, Meyer T, et al. Outcomes by prior transarterial chemoembolization (TACE) in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC) [abstract no. 704P plus poster]. Ann Oncol. 2018;29(Suppl 8).
25.
Zurück zum Zitat Kelley RK, Ryoo BY, Merle P, et al. Outcomes in patients (pts) who had received sorafenib (S) as the only prior systemic therapy in the phase 3 CELESTIAL trial of cabozantinib (C) versus placebo (P) in advanced hepatocellular carcinoma (HCC). [abstract no. 4088]. J Clin Oncol. 2018;36(Suppl). Kelley RK, Ryoo BY, Merle P, et al. Outcomes in patients (pts) who had received sorafenib (S) as the only prior systemic therapy in the phase 3 CELESTIAL trial of cabozantinib (C) versus placebo (P) in advanced hepatocellular carcinoma (HCC). [abstract no. 4088]. J Clin Oncol. 2018;36(Suppl).
26.
Zurück zum Zitat Zhou L, Liu XD, Sun M, et al. Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma. Oncogene. 2016;35(21):2687–97.CrossRefPubMed Zhou L, Liu XD, Sun M, et al. Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma. Oncogene. 2016;35(21):2687–97.CrossRefPubMed
27.
Zurück zum Zitat Shojaei F, Lee JH, Simmons BH, et al. HGF/c-Met acts as an alternative angiogenic pathway in sunitinib-resistant tumors. Cancer Res. 2010;70(24):10090–100.CrossRefPubMed Shojaei F, Lee JH, Simmons BH, et al. HGF/c-Met acts as an alternative angiogenic pathway in sunitinib-resistant tumors. Cancer Res. 2010;70(24):10090–100.CrossRefPubMed
29.
Zurück zum Zitat Ueki T, Fujimoto J, Suzuki T, et al. Expression of hepatocyte growth factor and its receptor, the c-met proto-oncogene, in hepatocellular carcinoma. Hepatology. 1997;25(3):619–23.CrossRefPubMed Ueki T, Fujimoto J, Suzuki T, et al. Expression of hepatocyte growth factor and its receptor, the c-met proto-oncogene, in hepatocellular carcinoma. Hepatology. 1997;25(3):619–23.CrossRefPubMed
30.
Zurück zum Zitat Liu J, Wang K, Yan Z, et al. Axl expression stratifies patients with poor prognosis after hepatectomy for hepatocellular carcinoma. PLoS ONE. 2016;11(5):e0154767.CrossRefPubMedPubMedCentral Liu J, Wang K, Yan Z, et al. Axl expression stratifies patients with poor prognosis after hepatectomy for hepatocellular carcinoma. PLoS ONE. 2016;11(5):e0154767.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Roskell N, Gregory J, Wisniewski T, et al. Indirect treatment comparisons of nivolumab versus regorafenib, cabozantinib and best supportive care after treatment with sorafenib for hepatocellular carcinoma [poster no. PCN17]. In: ISPOR Europe conference. 2018. Roskell N, Gregory J, Wisniewski T, et al. Indirect treatment comparisons of nivolumab versus regorafenib, cabozantinib and best supportive care after treatment with sorafenib for hepatocellular carcinoma [poster no. PCN17]. In: ISPOR Europe conference. 2018.
Metadaten
Titel
Cabozantinib: A Review in Advanced Hepatocellular Carcinoma
verfasst von
Emma D. Deeks
Publikationsdatum
14.02.2019
Verlag
Springer International Publishing
Erschienen in
Targeted Oncology / Ausgabe 1/2019
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-019-00622-y

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