Reference Detail

Ref Type

Journal Article

PMID

(32111729)

Authors

Okamura R, Kato S, Lee S, Jimenez RE, Sicklick JK, Kurzrock R

Title

ARID1A alterations function as a biomarker for longer progression-free survival after anti-PD-1/PD-L1 immunotherapy.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal for immunotherapy of cancer	8	1	2020 Feb		J Immunother Cancer

URL

Abstract Text

Several cancer types harbor alterations in the gene encoding AT-Rich Interactive Domain-containing protein 1A (ARID1A), but there are no approved therapies to address these alterations. Recent studies have shown that ARID1A deficiency compromises mismatch repair proteins. Herein, we analyzed 3403 patients who had tumor tissue next-generation sequencing.Among nine cancer subtypes with >5% prevalence of ARID1A alterations, microsatellite instability-high as well as high tumor mutational burden was significantly more frequent in ARID1A-altered versus ARID1A wild-type tumors (20% vs 0.9%, p<0.001; and 26% vs 8.4%, p<0.001, respectively). Median progression-free survival (PFS) after checkpoint blockade immunotherapy was significantly longer in the patients with ARID1A-altered tumors (n=46) than in those with ARID1A wild-type tumors (n=329) (11 months vs 4 months, p=0.006). Also, multivariate analysis showed that ARID1A alterations predicted longer PFS after checkpoint blockade (HR (95% CI), 0.61 (0.39 to 0.94), p=0.02) and this result was independent of microsatellite instability or mutational burden; median overall survival time was also longer in ARID1A-altered versus wild-type tumors (31 months vs 20 months), but did not reach statistical significance (p=0.13).Our findings suggest that ARID1A alterations merit further exploration as a novel biomarker correlating with better outcomes after checkpoint blockade immunotherapy.

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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
ARID1A mutant	endometrial cancer	predicted - sensitive	unspecified PD-L1 antibody	Clinical Study - Cohort	Actionable	In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in significantly longer median progression-free survival (4.6 vs 3.0 months, p=0.02) in patients with ARID1A-altered (n=10) endometrial cancer than in patients with ARID1A wild-type (n=13) tumors (PMID: 32111729).	32111729
ARID1A mutant	endometrial cancer	predicted - sensitive	unspecified PD-1 antibody	Clinical Study - Cohort	Actionable	In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in significantly longer median progression-free survival (4.6 vs 3.0 months, p=0.02) in patients with ARID1A-altered (n=10) endometrial cancer than in patients with ARID1A wild-type (n=13) tumors (PMID: 32111729).	32111729
ARID1A mutant	lung non-small cell carcinoma	predicted - sensitive	unspecified PD-1 antibody	Clinical Study - Cohort	Actionable	In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in longer but not statistically significant median progression-free survival (8.7 vs 4.6 months, p=0.53) in patients with ARID1A-altered (n=7) non-small cell lung cancer than in patients with ARID1A wild-type (n=104) tumors (PMID: 32111729).	32111729
ARID1A mutant	gastroesophageal cancer	predicted - sensitive	unspecified PD-1 antibody	Clinical Study - Cohort	Actionable	In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in longer median progression-free survival (11.4 vs 2.5 months, p=0.21) in patients with ARID1A-altered (n=5) gastroesophageal cancer than in patients with ARID1A wild-type (n=16) tumors (PMID: 32111729).	32111729
ARID1A mutant	colorectal cancer	predicted - sensitive	unspecified PD-1 antibody	Clinical Study - Cohort	Actionable	In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in significantly longer median progression-free survival (5.2 vs 2.1 months, p=0.005) in patients with ARID1A-altered (n=12) colorectal cancer than in patients with ARID1A wild-type (n=37) tumors (PMID: 32111729).	32111729
ARID1A mutant	Advanced Solid Tumor	predicted - sensitive	unspecified PD-L1 antibody	Clinical Study - Cohort	Actionable	In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in significantly longer median progression-free survival (PFS, 11 vs 4 months, p=0.006) in patients with ARID1A-altered (n=46) tumors than in patients with ARID1A wild-type (n=329) tumors, and improved overall survival (31 vs 20 months, p=0.13), ARID1A alterations predicted longer PFS (HR=0.61, p=0.02) after immune checkpoint inhibitor therapies independent of MSI or TMB status (PMID: 32111729).	32111729
ARID1A mutant	melanoma	predicted - sensitive	unspecified PD-1 antibody	Clinical Study - Cohort	Actionable	In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in longer median progression-free survival (45.4 vs 3.0 months, p=0.08) in patients with ARID1A-altered (n=6) melanoma than in patients with ARID1A wild-type (n=91) tumors (PMID: 32111729).	32111729
ARID1A mutant	gastroesophageal cancer	predicted - sensitive	unspecified PD-L1 antibody	Clinical Study - Cohort	Actionable	In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in longer median progression-free survival (11.4 vs 2.5 months, p=0.21) in patients with ARID1A-altered (n=5) gastroesophageal cancer than in patients with ARID1A wild-type (n=16) tumors (PMID: 32111729).	32111729
ARID1A mutant	lung non-small cell carcinoma	predicted - sensitive	unspecified PD-L1 antibody	Clinical Study - Cohort	Actionable	In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in longer but not statistically significant median progression-free survival (8.7 vs 4.6 months, p=0.53) in patients with ARID1A-altered (n=7) non-small cell lung cancer than in patients with ARID1A wild-type (n=104) tumors (PMID: 32111729).	32111729
ARID1A mutant	melanoma	predicted - sensitive	unspecified PD-L1 antibody	Clinical Study - Cohort	Actionable	In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in longer median progression-free survival (45.4 vs 3.0 months, p=0.08) in patients with ARID1A-altered (n=6) melanoma than in patients with ARID1A wild-type (n=91) tumors (PMID: 32111729).	32111729
ARID1A mutant	colorectal cancer	predicted - sensitive	unspecified PD-L1 antibody	Clinical Study - Cohort	Actionable	In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in significantly longer median progression-free survival (5.2 vs 2.1 months, p=0.005) in patients with ARID1A-altered (n=12) colorectal cancer than in patients with ARID1A wild-type (n=37) tumors (PMID: 32111729).	32111729
ARID1A mutant	Advanced Solid Tumor	predicted - sensitive	unspecified PD-1 antibody	Clinical Study - Cohort	Actionable	In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in significantly longer median progression-free survival (PFS, 11 vs 4 months, p=0.006) in patients with ARID1A-altered (n=46) tumors than in patients with ARID1A wild-type (n=329) tumors, and improved overall survival (31 vs 20 months, p=0.13), ARID1A alterations predicted longer PFS (HR=0.61, p=0.02) after immune checkpoint inhibitor therapies independent of MSI or TMB status (PMID: 32111729).	32111729