ARID1A alterations function as a biomarker for longer progression-free survival after anti-PD-1/PD-L1 immunotherapy
Background 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 analy...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/1/e000438.full |
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| author | Razelle Kurzrock Ryosuke Okamura Shumei Kato Suzanna Lee Rebecca E Jimenez Jason K Sicklick |
| author_facet | Razelle Kurzrock Ryosuke Okamura Shumei Kato Suzanna Lee Rebecca E Jimenez Jason K Sicklick |
| author_sort | Razelle Kurzrock |
| collection | DOAJ |
| description | Background 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.Findings 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).Conclusions Our findings suggest that ARID1A alterations merit further exploration as a novel biomarker correlating with better outcomes after checkpoint blockade immunotherapy. |
| format | Article |
| id | doaj-art-a3e99685d1364a2da58731a4e9e5b73d |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-a3e99685d1364a2da58731a4e9e5b73d2024-11-08T16:00:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2019-000438ARID1A alterations function as a biomarker for longer progression-free survival after anti-PD-1/PD-L1 immunotherapyRazelle Kurzrock0Ryosuke Okamura1Shumei Kato2Suzanna Lee3Rebecca E Jimenez4Jason K Sicklick5Medical College of Wisconsin, Milwaukee, Wisconsin, USA1 Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center, La Jolla, California, USA5Moores UCSD Cancer Center, La Jolla, CA, USA2University of California, San Diego, San Diego, CA, USA1 Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center, La Jolla, California, USA1 Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center, La Jolla, California, USABackground 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.Findings 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).Conclusions Our findings suggest that ARID1A alterations merit further exploration as a novel biomarker correlating with better outcomes after checkpoint blockade immunotherapy.https://jitc.bmj.com/content/8/1/e000438.full |
| spellingShingle | Razelle Kurzrock Ryosuke Okamura Shumei Kato Suzanna Lee Rebecca E Jimenez Jason K Sicklick ARID1A alterations function as a biomarker for longer progression-free survival after anti-PD-1/PD-L1 immunotherapy Journal for ImmunoTherapy of Cancer |
| title | ARID1A alterations function as a biomarker for longer progression-free survival after anti-PD-1/PD-L1 immunotherapy |
| title_full | ARID1A alterations function as a biomarker for longer progression-free survival after anti-PD-1/PD-L1 immunotherapy |
| title_fullStr | ARID1A alterations function as a biomarker for longer progression-free survival after anti-PD-1/PD-L1 immunotherapy |
| title_full_unstemmed | ARID1A alterations function as a biomarker for longer progression-free survival after anti-PD-1/PD-L1 immunotherapy |
| title_short | ARID1A alterations function as a biomarker for longer progression-free survival after anti-PD-1/PD-L1 immunotherapy |
| title_sort | arid1a alterations function as a biomarker for longer progression free survival after anti pd 1 pd l1 immunotherapy |
| url | https://jitc.bmj.com/content/8/1/e000438.full |
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