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Article: Pembrolizumab (Keytruda)

TitlePembrolizumab (Keytruda)
Authors
KeywordsLymphoma
Melanoma
Nonsmall cell lung cancer
PD1
PDL1
PDL2
Pembrolizumab
Solid tumors
Issue Date2016
Citation
Human Vaccines & Immunotherapeutics, 2016, v. 12 n. 11, p. 2777-2789 How to Cite?
AbstractAbstract The programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells. PD1 expression is an important mechanism contributing to the exhausted effector T-cell phenotype. The expression of PD1 on effector T-cells and PDL1 on neoplastic cells enables tumor cells to evade anti-tumor immunity. Blockade of PD1 is an important immunotherapeutic strategy for cancers. Pembrolizumab (Keytruda) is a humanized monoclonal anti-PD1 antibody that has been extensively investigated in numerous malignancies. In melanoma refractory to targeted therapy, pembrolizumab induced overall response rates (ORRs) of 21-34%. It was superior to another immune checkpoint inhibitor ipilimumab (Yervoy) in stage III/IV unresectable melanoma. In refractory non-small cell lung cancer (NSCLC), pembrolizumab induced ORRs of 19-25%. Based on these results, pembrolizumab was approved by the USA FDA for the treatment of advanced melanoma and NSCLC. Tumor cell PDL1 expression may be a valid response predictor. Molecular analysis also showed that tumors with high gene mutation burdens, which might result in the formation of more tumor-related neo-antigens, had better responses to pembrolizumab. In malignancies including lymphomas and other solid tumors, preliminary data showed that ORRs of around 20-50% could be achieved. Adverse events occurred in up to 60% of patients, but grade 3/4 toxicities were observed in <10% of cases. Immune-related adverse events including thyroid dysfunction, hepatitis and pneumonitis are more serious and may lead to cessation of treatment.
DescriptionLink to Free access
Persistent Identifierhttp://hdl.handle.net/10722/232071
ISSN
2020 Impact Factor: 3.452
2020 SCImago Journal Rankings: 1.043
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKwok, G-
dc.contributor.authorYau, TCC-
dc.contributor.authorChiu, WYJ-
dc.contributor.authorTse, EWC-
dc.contributor.authorKwong, YL-
dc.date.accessioned2016-09-20T05:27:30Z-
dc.date.available2016-09-20T05:27:30Z-
dc.date.issued2016-
dc.identifier.citationHuman Vaccines & Immunotherapeutics, 2016, v. 12 n. 11, p. 2777-2789-
dc.identifier.issn2164-5515-
dc.identifier.urihttp://hdl.handle.net/10722/232071-
dc.descriptionLink to Free access-
dc.description.abstractAbstract The programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells. PD1 expression is an important mechanism contributing to the exhausted effector T-cell phenotype. The expression of PD1 on effector T-cells and PDL1 on neoplastic cells enables tumor cells to evade anti-tumor immunity. Blockade of PD1 is an important immunotherapeutic strategy for cancers. Pembrolizumab (Keytruda) is a humanized monoclonal anti-PD1 antibody that has been extensively investigated in numerous malignancies. In melanoma refractory to targeted therapy, pembrolizumab induced overall response rates (ORRs) of 21-34%. It was superior to another immune checkpoint inhibitor ipilimumab (Yervoy) in stage III/IV unresectable melanoma. In refractory non-small cell lung cancer (NSCLC), pembrolizumab induced ORRs of 19-25%. Based on these results, pembrolizumab was approved by the USA FDA for the treatment of advanced melanoma and NSCLC. Tumor cell PDL1 expression may be a valid response predictor. Molecular analysis also showed that tumors with high gene mutation burdens, which might result in the formation of more tumor-related neo-antigens, had better responses to pembrolizumab. In malignancies including lymphomas and other solid tumors, preliminary data showed that ORRs of around 20-50% could be achieved. Adverse events occurred in up to 60% of patients, but grade 3/4 toxicities were observed in <10% of cases. Immune-related adverse events including thyroid dysfunction, hepatitis and pneumonitis are more serious and may lead to cessation of treatment.-
dc.languageeng-
dc.relation.ispartofHuman Vaccines & Immunotherapeutics-
dc.subjectLymphoma-
dc.subjectMelanoma-
dc.subjectNonsmall cell lung cancer-
dc.subjectPD1-
dc.subjectPDL1-
dc.subjectPDL2-
dc.subjectPembrolizumab-
dc.subjectSolid tumors-
dc.titlePembrolizumab (Keytruda)-
dc.typeArticle-
dc.identifier.emailYau, TCC: tyaucc@hku.hk-
dc.identifier.emailChiu, WYJ: jwychiu@hku.hk-
dc.identifier.emailTse, EWC: ewctse@hku.hk-
dc.identifier.emailKwong, YL: ylkwong@hkucc.hku.hk-
dc.identifier.authorityYau, TCC=rp01466-
dc.identifier.authorityChiu, WYJ=rp01917-
dc.identifier.authorityTse, EWC=rp00471-
dc.identifier.authorityKwong, YL=rp00358-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1080/21645515.2016.1199310-
dc.identifier.scopuseid_2-s2.0-85009785163-
dc.identifier.hkuros266596-
dc.identifier.volume12-
dc.identifier.issue11-
dc.identifier.spage2777-
dc.identifier.epage2789-
dc.identifier.eissn2164-554X-
dc.identifier.isiWOS:000388736900021-
dc.identifier.issnl2164-5515-

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