Reference Detail

Ref Type

Journal Article

PMID

(36252287)

Authors

Kim DW, Kim YC, Kovari BP, Chung V, Alese OB, El-Rayes BF, Li D, Park W, Kim RD

Title

Biomarker analysis from a phase II multi-institutional study of nivolumab in patients with advanced refractory biliary tract cancer.

Journal	Vol	Issue	Date	Pages	Journal Short Title
European journal of cancer (Oxford, England : 1990)	176		2022 Sep 28	171-180	Eur J Cancer

URL

Abstract Text

Our previous phase II study demonstrated that nivolumab provides modest but durable clinical efficacy in patients with refractory biliary tract cancer, suggesting the significant clinical benefit of nivolumab in selected patients and the necessity of predictive biomarkers. We evaluated clinicopathological characteristics and tumour microenvironment of the patients who were enrolled the trial to identify potential biomarkers.Baseline clinicopathological characteristics and pretreatment tumour samples were collected. The obtained tumour samples were assessed for whole exome sequencing, RNA sequencing and immunohistochemistry. Their correlations with clinical outcome were analysed.Pretreatment tumour evaluation revealed PD-L1 expression on tumour, CD8 T cell infiltration and high ratio of CD8 T cell/regulatory T cell in tumour microenvironment were significantly associated with prolonged progression-free survival (PFS), while PD-1 expression on lymphocytes and CD68 macrophages infiltration in tumour microenvironment had no predictive role. Asian patients (N = 3) had improved PFS and disease control rate compared with non-Asian (N = 54). A six-gene predictive model was constructed by evaluation of total 23,550 candidate genes from RNA sequencing of baseline tumour samples using LASSO-Cox regression analysis, and high score of the six-gene prediction model was associated with prolonged PFS.This study suggests that PD-L1 expression on tumour, CD8 T cell infiltration and high ratio of CD8/regulatory T cells and six-gene expression profile in tumour microenvironment may be potential predictive biomarkers of nivolumab in biliary tract cancers. Further studies are needed to confirm these findings.

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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 positive	biliary tract cancer	sensitive	Nivolumab	Phase II	Actionable	In a Phase II trial, baseline CD274 (PD-L1) expression was associated with increased median progression-free survival (PFS) in biliary tract cancer patients treated with Opdivo (nivolumab) compared to patients without CD274 (PD-L1) expression, with a median PFS of 19.8 months vs 2.4 months (P=0.0001) and 12-month PFS rate of 61% vs 5%, respectively (PMID: 36252287; NCT02829918).	36252287