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

TitleSecond-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial
Authors
Keywordscabozantinib
hepatocellular carcinoma
sorafenib
tyrosine kinase inhibitor
Issue Date2020
PublisherBMJ Publishing Group: BMJ Open Access. The Journal's web site is located at http://promotions.bmj.com/esmoopen/
Citation
ESMO Open, 2020, v. 5 n. 4, p. article no. e000714 How to Cite?
AbstractObjective: 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.
Persistent Identifierhttp://hdl.handle.net/10722/289438
ISSN
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKelley, RK-
dc.contributor.authorRyoo, BY-
dc.contributor.authorMerle, P-
dc.contributor.authorPark, JW-
dc.contributor.authorBolondi, L-
dc.contributor.authorChan, SL-
dc.contributor.authorLim, HY-
dc.contributor.authorBaron, AD-
dc.contributor.authorParnis, F-
dc.contributor.authorKnox, J-
dc.contributor.authorCattan, S-
dc.contributor.authorYau, T-
dc.contributor.authorLougheed, JC-
dc.contributor.authorMilwee, S-
dc.contributor.authorEl-Khoueiry, AB-
dc.contributor.authorCheng, AL-
dc.contributor.authorMeyer, T-
dc.contributor.authorAbou-Alfa, GK-
dc.date.accessioned2020-10-22T08:12:40Z-
dc.date.available2020-10-22T08:12:40Z-
dc.date.issued2020-
dc.identifier.citationESMO Open, 2020, v. 5 n. 4, p. article no. e000714-
dc.identifier.issn2059-7029-
dc.identifier.urihttp://hdl.handle.net/10722/289438-
dc.description.abstractObjective: 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.-
dc.languageeng-
dc.publisherBMJ Publishing Group: BMJ Open Access. The Journal's web site is located at http://promotions.bmj.com/esmoopen/-
dc.relation.ispartofESMO Open-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectcabozantinib-
dc.subjecthepatocellular carcinoma-
dc.subjectsorafenib-
dc.subjecttyrosine kinase inhibitor-
dc.titleSecond-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial-
dc.typeArticle-
dc.identifier.emailYau, T: tyaucc@hku.hk-
dc.identifier.authorityYau, T=rp01466-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1136/esmoopen-2020-000714-
dc.identifier.pmid32847838-
dc.identifier.pmcidPMC7451459-
dc.identifier.scopuseid_2-s2.0-85089984060-
dc.identifier.hkuros316114-
dc.identifier.volume5-
dc.identifier.issue4-
dc.identifier.spagearticle no. e000714-
dc.identifier.epagearticle no. e000714-
dc.identifier.isiWOS:000567378100008-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl2059-7029-

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