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      Survival improvement for patients with metastatic colorectal cancer over twenty years

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          Abstract

          Over the past two decades of successive clinical trials in metastatic colorectal cancer (CRC), the median overall survival of both control and experimental arms has steadily improved. However, the incremental change in survival for metastatic CRC patients not treated on trial has not yet been quantified. We performed a retrospective review of 1420 patients with de novo metastatic CRC who received their primary treatment at the University of Texas M.D. Anderson Cancer Center (UTMDACC) from 2004 through 2019. Median OS was roughly stable for patients diagnosed between 2004 and 2012 (22.6 months) but since has steadily improved for those diagnosed in 2013 to 2015 (28.8 months), and 2016 to 2019 (32.4 months). Likewise, 5-year survival rate has increased from 15.7% for patients diagnosed from 2004 to 2006 to 26% for those diagnosed from 2013 to 2015. Notably, survival improved for patients with BRAF V600E mutant as well as microsatellite unstable (MSI-H) tumors. Multivariate regression analysis identified surgical resection of liver metastasis (HR = 0.26, 95% CI, 0.19–0.37), use of immunotherapy (HR = 0.44, 95% CI, 0.29–0.67) and use of third line chemotherapy (regorafenib or trifluridine/tipiracil, HR = 0.74, 95% CI, 0.58–0.95), but not year of diagnosis (HR = 0.99, 95% CI, 0.98–1), as associated with better survival, suggesting that increased use of these therapies are the drivers of the observed improvement in survival.

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          Most cited references63

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          PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.

          Somatic mutations have the potential to encode "non-self" immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade.
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            Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

            The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers' tissue of origin.
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              Pembrolizumab in Microsatellite-Instability–High Advanced Colorectal Cancer

              Programmed death 1 (PD-1) blockade has clinical benefit in microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) tumors after previous therapy. The efficacy of PD-1 blockade as compared with chemotherapy as first-line therapy for MSI-H-dMMR advanced or metastatic colorectal cancer is unknown.
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                Author and article information

                Contributors
                Jshen8@mdanderson.org
                Journal
                NPJ Precis Oncol
                NPJ Precis Oncol
                NPJ Precision Oncology
                Nature Publishing Group UK (London )
                2397-768X
                13 February 2023
                13 February 2023
                2023
                : 7
                : 16
                Affiliations
                [1 ]GRID grid.240145.6, ISNI 0000 0001 2291 4776, Department of Gastrointestinal Medical Oncology, , The University of Texas MD Anderson Cancer Center, ; Houston, TX USA
                [2 ]GRID grid.240145.6, ISNI 0000 0001 2291 4776, Department of Surgical Oncology, , The University of Texas MD Anderson Cancer Center, ; Houston, TX USA
                [3 ]GRID grid.240145.6, ISNI 0000 0001 2291 4776, Department of Biostatistics, , The University of Texas MD Anderson Cancer Center, ; Houston, TX USA
                Author information
                http://orcid.org/0000-0001-8075-765X
                http://orcid.org/0000-0001-7761-8149
                http://orcid.org/0000-0002-9642-0338
                http://orcid.org/0000-0002-0783-3959
                http://orcid.org/0000-0002-7887-8484
                http://orcid.org/0000-0003-1311-4173
                http://orcid.org/0000-0001-8238-8552
                http://orcid.org/0000-0003-2986-3224
                http://orcid.org/0000-0003-4588-2775
                Article
                353
                10.1038/s41698-023-00353-4
                9925745
                36781990
                bff8cea4-57ad-465f-8ebe-a40594ab3409
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 12 May 2022
                : 16 January 2023
                Funding
                Funded by: FundRef https://doi.org/10.13039/100004917, Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas);
                Funded by: FundRef https://doi.org/10.13039/100000054, U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI);
                Award ID: SPORE P50CA221707
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2023

                colorectal cancer,prognostic markers,chemotherapy
                colorectal cancer, prognostic markers, chemotherapy

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