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Ref Type Journal Article
PMID (29902298)
Authors Goodman AM, Piccioni D, Kato S, Boichard A, Wang HY, Frampton G, Lippman SM, Connelly C, Fabrizio D, Miller V, Sicklick JK, Kurzrock R
Title Prevalence of PDL1 Amplification and Preliminary Response to Immune Checkpoint Blockade in Solid Tumors.
URL
Abstract Text Copy number alterations in programmed cell death ligand 1 (PDL1 or CD274), programmed cell death 1 ligand 2 (PDCD1LG2 or PDL2), and Janus kinase 2 (JAK2) genes (chromosome 9p24.1) characterize Hodgkin lymphoma, resulting in high response rates to programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) blockade. The prevalence and utility of PDL1 amplification as a response biomarker to PD-1/PD-L1 blockade are unknown in other tumors.To examine the prevalence of PDL1 amplification and its utility as a response biomarker to PD-1/PD-L1 blockade in solid tumors.This retrospective study (October 1, 2012, to October 1, 2017) used a deidentified tumor database from a commercial company and annotated clinical records from a subset of patients treated at a university tertiary referral center. The study analyzed 118 187 tumors from the deidentified database, including a clinically annotated subgroup of 2039 malignant tumors.Comprehensive genomic profiling was performed on all samples to determine PDL1 amplification, microsatellite instability, and tumor mutational burden (TMB). A subset of patients was treated with PD-1/PD-L1 blockade.The prevalence of PDL1 amplification was determined among 118 187 patient samples that underwent next-generation sequencing. Solid tumors treated with checkpoint blockade were evaluated for response and progression-free survival (PFS).Of the 118 187 deidentified tumor samples, PDL1 amplifications were identified in 843 (0.7%), including more than 100 types of solid tumors. Most PDL1-amplified tumors (84.8%) had a low to intermediate TMB. PDL1 amplification did not always correlate with high-positive PD-L1 expression by immunohistochemical analysis. Six of 9 patients (66.7%) from 1 center with PDL1-amplified solid tumors had objective responses after checkpoint blockade administration. The median PFS among all treated patients was 15.2 months. Responders included 1 patient with glioblastoma (PFS, ≥5.2 months), 2 patients with head and neck squamous cell cancer (PFS, ≥9 and 15.2 months), 2 patients with metastatic basal cell cancer (PFS, 3.8 and ≥24.1 months), and 1 patient with urothelial cancer (PFS, ≥17.8 months).The results of this study suggest that PDL1 amplification occurs in a small subset of malignant tumors. Additional large-scale, prospective studies of PDL1-amplified cancers are warranted to confirm the responses to checkpoint blockade described herein, even in the absence of microsatellite instability, high PD-L1 expression, and a high TMB.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
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
CD274 amp Advanced Solid Tumor predicted - sensitive unspecified PD-1 antibody Case Reports/Case Series Actionable In a clinical study, 66.7% (6/9) of advanced solid tumor patients harboring CD274 amplification demonstrated an objective response when treated with a PD-1/PD-L1 monotherapy (5 patients), a PD-1/PD-L1 therapy combined with an investigational drug (3 patients), or a combination of an anti-PD-1 and anti-CTLA4 therapy (1 patient) (PMID: 29902298). 29902298
CD274 amp Advanced Solid Tumor predicted - sensitive unspecified PD-L1 antibody Clinical Study Actionable In a clinical study, 66.7% (6/9) of advanced solid tumor patients harboring CD274 amplification demonstrated an objective response when treated with a PD-1/PD-L1 monotherapy (5 patients), a PD-1/PD-L1 therapy combined with an investigational drug (3 patients), or a combination of an anti-PD-1 and anti-CTLA4 therapy (1 patient) (PMID: 29902298). 29902298