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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 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 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 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
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 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 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 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 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 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 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 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 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