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Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial

OBJECTIVE: In the phase 3 CELESTIAL trial, cabozantinib improved overall survival (OS) and progression-free survival (PFS) compared with placebo in patients with previously treated advanced hepatocellular carcinoma (HCC). This subgroup analysis evaluated cabozantinib in patients who had received sor...

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Autores principales: Kelley, Robin Kate, Ryoo, Baek-Yeol, Merle, Philippe, Park, Joong-Won, Bolondi, Luigi, Chan, Stephen L, Lim, Ho Yeong, Baron, Ari D, Parnis, Francis, Knox, Jennifer, Cattan, Stéphane, Yau, Thomas, Lougheed, Julie C, Milwee, Steven, El-Khoueiry, Anthony B, Cheng, Ann-Lii, Meyer, Tim, Abou-Alfa, Ghassan K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451459/
https://www.ncbi.nlm.nih.gov/pubmed/32847838
http://dx.doi.org/10.1136/esmoopen-2020-000714
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author Kelley, Robin Kate
Ryoo, Baek-Yeol
Merle, Philippe
Park, Joong-Won
Bolondi, Luigi
Chan, Stephen L
Lim, Ho Yeong
Baron, Ari D
Parnis, Francis
Knox, Jennifer
Cattan, Stéphane
Yau, Thomas
Lougheed, Julie C
Milwee, Steven
El-Khoueiry, Anthony B
Cheng, Ann-Lii
Meyer, Tim
Abou-Alfa, Ghassan K
author_facet Kelley, Robin Kate
Ryoo, Baek-Yeol
Merle, Philippe
Park, Joong-Won
Bolondi, Luigi
Chan, Stephen L
Lim, Ho Yeong
Baron, Ari D
Parnis, Francis
Knox, Jennifer
Cattan, Stéphane
Yau, Thomas
Lougheed, Julie C
Milwee, Steven
El-Khoueiry, Anthony B
Cheng, Ann-Lii
Meyer, Tim
Abou-Alfa, Ghassan K
author_sort Kelley, Robin Kate
collection PubMed
description OBJECTIVE: In the phase 3 CELESTIAL trial, cabozantinib improved overall survival (OS) and progression-free survival (PFS) compared with placebo in patients with previously treated advanced hepatocellular carcinoma (HCC). This subgroup analysis evaluated cabozantinib in patients who had received sorafenib as the only prior systemic therapy. METHODS: CELESTIAL randomised (2:1) patients with advanced HCC and Child–Pugh class A liver function to treatment with cabozantinib (60 mg daily) or placebo. Eligibility required prior treatment with sorafenib, and patients could have received ≤2 prior systemic regimens. The primary endpoint was OS. Outcomes in patients who had received sorafenib as the only prior therapy were analysed by duration of prior sorafenib (<3 months, 3 to <6 months and ≥6 months). RESULTS: Of patients who had received only prior sorafenib, 331 were randomised to cabozantinib and 164 to placebo; 136 patients had received sorafenib for <3 months, 141 for 3 to <6 months and 217 for ≥6 months. Cabozantinib improved OS relative to placebo in the overall second-line population who had received only prior sorafenib (median 11.3 vs 7.2 months; HR=0.70, 95% CI 0.55 to 0.88). This improvement was maintained in analyses by prior sorafenib duration with longer duration generally corresponding to longer median OS—median OS 8.9 vs 6.9 months (HR=0.72, 95% CI 0.47 to 1.10) for prior sorafenib <3 months, 11.5 vs 6.5 months (HR=0.65, 95% CI 0.43 to 1.00) for 3 to <6 months and 12.3 vs 9.2 months (HR=0.82, 95% CI 0.58 to 1.16) for ≥6 months. Cabozantinib also improved PFS in all duration subgroups. Safety data were consistent with the overall study population. CONCLUSION: Cabozantinib improved efficacy outcomes versus placebo in the second-line population who had received only prior sorafenib irrespective of duration of prior sorafenib treatment, further supporting the utility of cabozantinib in the evolving treatment landscape of HCC. CLINICAL TRIAL NUMBER: NCT01908426.
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spelling pubmed-74514592020-09-02 Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial Kelley, Robin Kate Ryoo, Baek-Yeol Merle, Philippe Park, Joong-Won Bolondi, Luigi Chan, Stephen L Lim, Ho Yeong Baron, Ari D Parnis, Francis Knox, Jennifer Cattan, Stéphane Yau, Thomas Lougheed, Julie C Milwee, Steven El-Khoueiry, Anthony B Cheng, Ann-Lii Meyer, Tim Abou-Alfa, Ghassan K ESMO Open Original Research OBJECTIVE: In the phase 3 CELESTIAL trial, cabozantinib improved overall survival (OS) and progression-free survival (PFS) compared with placebo in patients with previously treated advanced hepatocellular carcinoma (HCC). This subgroup analysis evaluated cabozantinib in patients who had received sorafenib as the only prior systemic therapy. METHODS: CELESTIAL randomised (2:1) patients with advanced HCC and Child–Pugh class A liver function to treatment with cabozantinib (60 mg daily) or placebo. Eligibility required prior treatment with sorafenib, and patients could have received ≤2 prior systemic regimens. The primary endpoint was OS. Outcomes in patients who had received sorafenib as the only prior therapy were analysed by duration of prior sorafenib (<3 months, 3 to <6 months and ≥6 months). RESULTS: Of patients who had received only prior sorafenib, 331 were randomised to cabozantinib and 164 to placebo; 136 patients had received sorafenib for <3 months, 141 for 3 to <6 months and 217 for ≥6 months. Cabozantinib improved OS relative to placebo in the overall second-line population who had received only prior sorafenib (median 11.3 vs 7.2 months; HR=0.70, 95% CI 0.55 to 0.88). This improvement was maintained in analyses by prior sorafenib duration with longer duration generally corresponding to longer median OS—median OS 8.9 vs 6.9 months (HR=0.72, 95% CI 0.47 to 1.10) for prior sorafenib <3 months, 11.5 vs 6.5 months (HR=0.65, 95% CI 0.43 to 1.00) for 3 to <6 months and 12.3 vs 9.2 months (HR=0.82, 95% CI 0.58 to 1.16) for ≥6 months. Cabozantinib also improved PFS in all duration subgroups. Safety data were consistent with the overall study population. CONCLUSION: Cabozantinib improved efficacy outcomes versus placebo in the second-line population who had received only prior sorafenib irrespective of duration of prior sorafenib treatment, further supporting the utility of cabozantinib in the evolving treatment landscape of HCC. CLINICAL TRIAL NUMBER: NCT01908426. BMJ Publishing Group 2020-08-26 /pmc/articles/PMC7451459/ /pubmed/32847838 http://dx.doi.org/10.1136/esmoopen-2020-000714 Text en © Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology. http://creativecommons.org/licenses/by-nc/4.0/ http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, any changes made are indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Original Research
Kelley, Robin Kate
Ryoo, Baek-Yeol
Merle, Philippe
Park, Joong-Won
Bolondi, Luigi
Chan, Stephen L
Lim, Ho Yeong
Baron, Ari D
Parnis, Francis
Knox, Jennifer
Cattan, Stéphane
Yau, Thomas
Lougheed, Julie C
Milwee, Steven
El-Khoueiry, Anthony B
Cheng, Ann-Lii
Meyer, Tim
Abou-Alfa, Ghassan K
Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial
title Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial
title_full Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial
title_fullStr Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial
title_full_unstemmed Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial
title_short Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial
title_sort second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 celestial trial
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451459/
https://www.ncbi.nlm.nih.gov/pubmed/32847838
http://dx.doi.org/10.1136/esmoopen-2020-000714
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