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Ref Type Journal Article
PMID (31415061)
Authors Wang F, Zhao Q, Wang YN, Jin Y, He MM, Liu ZX, Xu RH
Title Evaluation of POLE and POLD1 Mutations as Biomarkers for Immunotherapy Outcomes Across Multiple Cancer Types.
Journal Vol Issue Date Pages Journal Short Title
JAMA oncology 5 10 2019 Oct 01 1504-1506 JAMA Oncol
URL
Abstract Text This cohort study analyzes the medical records of 47 721 patients with various cancer types with POLE/POLD1 mutations to evaluate whether the mutations were associated with immunotherapy outcomes.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
POLD1 NCBI CDC2|CRCS10|IMD120|MDPL|POLD POLD1, DNA polymerase delta 1, catalytic subunit, is the catalytic subunit and the largest of four subunits that form the DNA polymerase delta holoenzyme, which mediates DNA replication (PMID: 27320729) and repair (PMID: 30625304). Germline and somatic mutations in POLD1 have been identified in a variety of human cancers (PMID: 27320729), including colorectal cancer (PMID: 31769227) and lung cancer (PMID: 31673068), and may be associated with high tumor mutational burden and response to immunotherapy (PMID: 31741177, PMID: 31673068, PMID: 31415061, PMID: 30524909). Tumor suppressor
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
POLE mutant Advanced Solid Tumor predicted - sensitive unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). 31415061
POLD1 mutant Advanced Solid Tumor predicted - sensitive unspecified CTLA4 antibody Clinical Study - Cohort Actionable In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). 31415061
POLD1 mutant Advanced Solid Tumor predicted - sensitive unspecified PD-L1 antibody Clinical Study - Cohort Actionable In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). 31415061
POLD1 mutant Advanced Solid Tumor predicted - sensitive unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). 31415061
POLE mutant Advanced Solid Tumor predicted - sensitive unspecified PD-L1 antibody Clinical Study - Cohort Actionable In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). 31415061
POLE mutant Advanced Solid Tumor predicted - sensitive unspecified CTLA4 antibody Clinical Study - Cohort Actionable In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). 31415061