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Article: Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial

TitlePembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial
Authors
Issue Date2020
PublisherAmerican Society of Clinical Oncology. The Journal's web site is located at http://www.jco.org/
Citation
Journal of Clinical Oncology, 2020, v. 38 n. 3, p. 193-202 How to Cite?
AbstractPURPOSE: Pembrolizumab demonstrated antitumor activity and safety in the phase II KEYNOTE-224 trial in previously treated patients with advanced hepatocellular carcinoma (HCC). KEYNOTE-240 evaluated the efficacy and safety of pembrolizumab in this population. PATIENTS AND METHODS: This randomized, double-blind, phase III study was conducted at 119 medical centers in 27 countries. Eligible patients with advanced HCC, previously treated with sorafenib, were randomly assigned at a two-to-one ratio to receive pembrolizumab plus best supportive care (BSC) or placebo plus BSC. Primary end points were overall survival (OS) and progression-free survival (PFS; one-sided significance thresholds, P = .0174 [final analysis] and P = .002 [first interim analysis], respectively). Safety was assessed in all patients who received ≥ 1 dose of study drug. RESULTS: Between May 31, 2016, and November 23, 2017, 413 patients were randomly assigned. As of January 2, 2019, median follow-up was 13.8 months for pembrolizumab and 10.6 months for placebo. Median OS was 13.9 months (95% CI, 11.6 to 16.0 months) for pembrolizumab versus 10.6 months (95% CI, 8.3 to 13.5 months) for placebo (hazard ratio [HR], 0.781; 95% CI, 0.611 to 0.998; P = .0238). Median PFS for pembrolizumab was 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 2.5 to 4.1 months) for placebo at the first interim analysis (HR, 0.775; 95% CI, 0.609 to 0.987; P = .0186) and 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 1.6 to 3.0 months) at final analysis (HR, 0.718; 95% CI, 0.570 to 0.904; P = .0022). Grade 3 or higher adverse events occurred in 147 (52.7%) and 62 patients (46.3%) for pembrolizumab versus placebo; those that were treatment related occurred in 52 (18.6%) and 10 patients (7.5%), respectively. No hepatitis C or B flares were identified. CONCLUSION: In this study, OS and PFS did not reach statistical significance per specified criteria. The results are consistent with those of KEYNOTE-224, supporting a favorable risk-to-benefit ratio for pembrolizumab in this population.
Persistent Identifierhttp://hdl.handle.net/10722/279461
ISSN
2017 Impact Factor: 26.36
2015 SCImago Journal Rankings: 9.204

 

DC FieldValueLanguage
dc.contributor.authorFinn, RS-
dc.contributor.authorRyoo, B-Y-
dc.contributor.authorMerle, P-
dc.contributor.authorKudo, M-
dc.contributor.authorBouattour, M-
dc.contributor.authorLim, HY-
dc.contributor.authorBreder, V-
dc.contributor.authorEdeline, J-
dc.contributor.authorChao, Y-
dc.contributor.authorOgasawara, S-
dc.contributor.authorYau, T-
dc.contributor.authorGarrido, M-
dc.contributor.authorChan, SL-
dc.contributor.authorKnox, J-
dc.contributor.authorDaniele, B-
dc.contributor.authorEbbinghaus, SW-
dc.contributor.authorChen, E-
dc.contributor.authorSiegel, AB-
dc.contributor.authorZhu, AX-
dc.contributor.authorCheng, A-L-
dc.contributor.authorThe KEYNOTE-240 investigators-
dc.date.accessioned2019-11-01T07:17:49Z-
dc.date.available2019-11-01T07:17:49Z-
dc.date.issued2020-
dc.identifier.citationJournal of Clinical Oncology, 2020, v. 38 n. 3, p. 193-202-
dc.identifier.issn0732-183X-
dc.identifier.urihttp://hdl.handle.net/10722/279461-
dc.description.abstractPURPOSE: Pembrolizumab demonstrated antitumor activity and safety in the phase II KEYNOTE-224 trial in previously treated patients with advanced hepatocellular carcinoma (HCC). KEYNOTE-240 evaluated the efficacy and safety of pembrolizumab in this population. PATIENTS AND METHODS: This randomized, double-blind, phase III study was conducted at 119 medical centers in 27 countries. Eligible patients with advanced HCC, previously treated with sorafenib, were randomly assigned at a two-to-one ratio to receive pembrolizumab plus best supportive care (BSC) or placebo plus BSC. Primary end points were overall survival (OS) and progression-free survival (PFS; one-sided significance thresholds, P = .0174 [final analysis] and P = .002 [first interim analysis], respectively). Safety was assessed in all patients who received ≥ 1 dose of study drug. RESULTS: Between May 31, 2016, and November 23, 2017, 413 patients were randomly assigned. As of January 2, 2019, median follow-up was 13.8 months for pembrolizumab and 10.6 months for placebo. Median OS was 13.9 months (95% CI, 11.6 to 16.0 months) for pembrolizumab versus 10.6 months (95% CI, 8.3 to 13.5 months) for placebo (hazard ratio [HR], 0.781; 95% CI, 0.611 to 0.998; P = .0238). Median PFS for pembrolizumab was 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 2.5 to 4.1 months) for placebo at the first interim analysis (HR, 0.775; 95% CI, 0.609 to 0.987; P = .0186) and 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 1.6 to 3.0 months) at final analysis (HR, 0.718; 95% CI, 0.570 to 0.904; P = .0022). Grade 3 or higher adverse events occurred in 147 (52.7%) and 62 patients (46.3%) for pembrolizumab versus placebo; those that were treatment related occurred in 52 (18.6%) and 10 patients (7.5%), respectively. No hepatitis C or B flares were identified. CONCLUSION: In this study, OS and PFS did not reach statistical significance per specified criteria. The results are consistent with those of KEYNOTE-224, supporting a favorable risk-to-benefit ratio for pembrolizumab in this population.-
dc.languageeng-
dc.publisherAmerican Society of Clinical Oncology. The Journal's web site is located at http://www.jco.org/-
dc.relation.ispartofJournal of Clinical Oncology-
dc.titlePembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial-
dc.typeArticle-
dc.identifier.emailYau, T: tyaucc@hku.hk-
dc.identifier.authorityYau, T=rp01466-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1200/JCO.19.01307-
dc.identifier.pmid31790344-
dc.identifier.hkuros308502-
dc.identifier.volume38-
dc.identifier.issue3-
dc.identifier.spage193-
dc.identifier.epage202-
dc.publisher.placeUnited States-

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