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Article: Pharmacodynamic biomarkers predictive of survival benefit with lenvatinib in unresectable hepatocellular carcinoma: from the phase III REFLECT study

TitlePharmacodynamic biomarkers predictive of survival benefit with lenvatinib in unresectable hepatocellular carcinoma: from the phase III REFLECT study
Authors
Issue Date2021
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/
Citation
Clinical Cancer Research, 2021, v. 27 n. 17, p. 4848-4858 How to Cite?
AbstractPurpose: In REFLECT, lenvatinib demonstrated an effect on overall survival (OS) by confirmation of noninferiority to sorafenib in unresectable hepatocellular carcinoma. This analysis assessed correlations between serum or tissue biomarkers and efficacy outcomes from REFLECT. Experimental Design: Serum biomarkers (VEGF, ANG2, FGF19, FGF21, and FGF23) were measured by ELISA. Gene expression in tumor tissues was measured by the nCounter PanCancer Pathways Panel. Pharmacodynamic changes in serum biomarker levels from baseline, and associations of clinical outcomes with baseline biomarker levels, were evaluated. Results: Four hundred and seven patients were included in the serum analysis set (lenvatinib n = 279, sorafenib n = 128); 58 patients were included in the gene-expression analysis set (lenvatinib n = 34, sorafenib n = 24). Both treatments were associated with increases in VEGF; only lenvatinib was associated with increases in FGF19 and FGF23 at all time points. Lenvatinib-treated responders had greater increases in FGF19 and FGF23 versus nonresponders at cycle 4, day 1 (FGF19: 55.2% vs. 18.3%, P = 0.014; FGF23: 48.4% vs. 16.4%, P = 0.0022, respectively). Higher baseline VEGF, ANG2, and FGF21 correlated with shorter OS in both treatment groups. OS was longer for lenvatinib than sorafenib [median, 10.9 vs. 6.8 months, respectively; HR, 0.53; 95% confidence interval (CI), 0.33–0.85; P-interaction = 0.0397] with higher baseline FGF21. In tumor tissue biomarker analysis, VEGF/FGF-enriched groups showed improved OS with lenvatinib versus the intermediate VEGF/FGF group (HR, 0.39; 95% CI, 0.16–0.91; P = 0.0253). Conclusions: Higher baseline levels of VEGF, FGF21, and ANG2 may be prognostic for shorter OS. Higher baseline FGF21 may be predictive for longer OS with lenvatinib compared with sorafenib, but this needs confirmation.
Persistent Identifierhttp://hdl.handle.net/10722/310123
ISSN
2023 Impact Factor: 10.0
2023 SCImago Journal Rankings: 4.623
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFinn, RS-
dc.contributor.authorKudo, M-
dc.contributor.authorCheng, AL-
dc.contributor.authorWyrwicz, L-
dc.contributor.authorNgan, RKC-
dc.contributor.authorBlanc, JF-
dc.contributor.authorBaron, AD-
dc.contributor.authorVogel, A-
dc.contributor.authorIkeda, M-
dc.contributor.authorPiscaglia, F-
dc.contributor.authorHan, KH-
dc.contributor.authorQin, S-
dc.contributor.authorMinoshima, Y-
dc.contributor.authorKanekiyo, M-
dc.contributor.authorRen, M-
dc.contributor.authorDairiki, R-
dc.contributor.authorTamai, T-
dc.contributor.authorDutcus, CE-
dc.contributor.authorIkezawa, H-
dc.contributor.authorFunahashi, Y-
dc.contributor.authorEvans, TRJ-
dc.date.accessioned2022-01-24T02:24:10Z-
dc.date.available2022-01-24T02:24:10Z-
dc.date.issued2021-
dc.identifier.citationClinical Cancer Research, 2021, v. 27 n. 17, p. 4848-4858-
dc.identifier.issn1078-0432-
dc.identifier.urihttp://hdl.handle.net/10722/310123-
dc.description.abstractPurpose: In REFLECT, lenvatinib demonstrated an effect on overall survival (OS) by confirmation of noninferiority to sorafenib in unresectable hepatocellular carcinoma. This analysis assessed correlations between serum or tissue biomarkers and efficacy outcomes from REFLECT. Experimental Design: Serum biomarkers (VEGF, ANG2, FGF19, FGF21, and FGF23) were measured by ELISA. Gene expression in tumor tissues was measured by the nCounter PanCancer Pathways Panel. Pharmacodynamic changes in serum biomarker levels from baseline, and associations of clinical outcomes with baseline biomarker levels, were evaluated. Results: Four hundred and seven patients were included in the serum analysis set (lenvatinib n = 279, sorafenib n = 128); 58 patients were included in the gene-expression analysis set (lenvatinib n = 34, sorafenib n = 24). Both treatments were associated with increases in VEGF; only lenvatinib was associated with increases in FGF19 and FGF23 at all time points. Lenvatinib-treated responders had greater increases in FGF19 and FGF23 versus nonresponders at cycle 4, day 1 (FGF19: 55.2% vs. 18.3%, P = 0.014; FGF23: 48.4% vs. 16.4%, P = 0.0022, respectively). Higher baseline VEGF, ANG2, and FGF21 correlated with shorter OS in both treatment groups. OS was longer for lenvatinib than sorafenib [median, 10.9 vs. 6.8 months, respectively; HR, 0.53; 95% confidence interval (CI), 0.33–0.85; P-interaction = 0.0397] with higher baseline FGF21. In tumor tissue biomarker analysis, VEGF/FGF-enriched groups showed improved OS with lenvatinib versus the intermediate VEGF/FGF group (HR, 0.39; 95% CI, 0.16–0.91; P = 0.0253). Conclusions: Higher baseline levels of VEGF, FGF21, and ANG2 may be prognostic for shorter OS. Higher baseline FGF21 may be predictive for longer OS with lenvatinib compared with sorafenib, but this needs confirmation.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/-
dc.relation.ispartofClinical Cancer Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titlePharmacodynamic biomarkers predictive of survival benefit with lenvatinib in unresectable hepatocellular carcinoma: from the phase III REFLECT study-
dc.typeArticle-
dc.identifier.emailNgan, RKC: rkcngan@hku.hk-
dc.identifier.authorityNgan, RKC=rp02371-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1158/1078-0432.CCR-20-4219-
dc.identifier.pmid34108184-
dc.identifier.scopuseid_2-s2.0-85114193226-
dc.identifier.hkuros331448-
dc.identifier.volume27-
dc.identifier.issue17-
dc.identifier.spage4848-
dc.identifier.epage4858-
dc.identifier.isiWOS:000692914500021-
dc.publisher.placeUnited States-

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