DNA mismatch repair and microsatellite instability in colorectal tumors: An observational study in the Veterans Affairs Health Care System.

Authors

Zachary Klaassen

Zachary William Abraham Klaassen

Division of Urology, Medical College of Georgia at Augusta University, Georgia Cancer Center, Augusta, GA

Zachary William Abraham Klaassen , Justin Waller , Lin Gu , Amanda M. De Hoedt , Tongtong Wang , Mayur Amonkar , Deepti Aurora-Garg , Kai-Li Liaw , Amy Wehn , Daniel Albo , Stephen J. Freedland

Organizations

Division of Urology, Medical College of Georgia at Augusta University, Georgia Cancer Center, Augusta, GA, Durham VA Health Care System, Durham, NC, Durham Veterans Affairs Health Care System, Durham, NC, Section of Urology, Durham Veterans Affairs Health Care System, Durham, NC, Center for Observational and Real-World Evidence, Merck & Co., Inc., Kenilworth, NJ, GlaxoSmithKline, Collegeville, PA, Merck & Co., Inc., Kenilworth, NJ, Merck & Co., Inc., Upper Gwynedd, PA, Research Science, Merck & Co., Inc., Kenilworth, NJ, Augusta University Medical Center, Augusta, GA, Veterans Affairs Health Care System, Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Durham, NC

Research Funding

Pharmaceutical/Biotech Company
Merck

Background: Microsatellite instability-high (MSI-H) and deficient mismatch repair (dMMR) cancers exhibit high mutational load and are observed in colorectal carcinomas (CRC). The objectives of this study were to determine the proportion of MSI-H/dMMR in CRC and to describe clinical and demographic characteristics among MSI-H/dMMR and non-MSI-H/dMMR CRC patients receiving standard of care in an equal access health care system. Methods: Using the Veteran Affairs (VA) Healthcare system data, we conducted a retrospective study of patients, aged ≥18 years old, diagnosed with CRC who underwent MSI/MMR testing from January 1, 2010 to December 31, 2018. MSI/MMR testing was defined as having received an MSI status determined by polymerase chain reaction and/or next-generation sequencing test or an MMR status determined by immunohistochemistry test. Median and interquartile range (IQR) were calculated for continuous variables while frequencies and percentages were calculated for categorical variables. Results: A total of 291 patients diagnosed with CRC who underwent MSI/MMR testing between 2010-2018 were identified from VA centers. The majority of patients were white (69.8%) and male (95.5%), with median (IQR) age of 65 (56-70) years at diagnosis. Sixty-four (22.0%) patients had stage I CRC at diagnosis, 84 (28.9%) stage II, 87 (29.9%) stage III, and 45 (15.5%) stage IV; 11 (3.7%) had no stage information. Fifty-four (18.6%) patients were reported to have MSI-H and/or dMMR CRC, with rates similar for MSI-H [17.4% (21/121)] vs. dMMR [19.7% (44/223)] alone. The proportion of MSI-H/dMMR varied by CRC stage, and was more common in stage II (26%) and stage III (23%) than in stage IV (6%). Patients were similar between MSI-H/dMMR and non-MSI-H/dMMR with regards to age at diagnosis, gender, race, and ethnicity. Of 54 patients with MSI-H/dMMR CRC, three had metastatic CRC (mCRC) at diagnosis and seven progressed to mCRC. Among 51 MSI-H/dMMR patients without metastatic disease at diagnosis, 18 (35%) underwent chemotherapy and 44 (86%) underwent curative surgery. A similar pattern was also observed among non-MSI-H/dMMR CRC patients. Conclusions: In this real-world observational study in a VA population, we found MSI-H/dMMR was present in 18.6% of CRC patients who received MSI testing, highest in stage II (26%) and stage III (23%) and lowest in stage IV (6%) disease. Results are consistent with published estimates seen across other populations and geographies. Additional research is needed in larger cohorts of patients to further assess utilization patterns and real-world clinical outcomes of newer treatments (immunotherapies) approved for MSI-H/dMMR CRC.

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Publication Only: Gastrointestinal Cancer—Colorectal and Anal

Track

Gastrointestinal Cancer—Colorectal and Anal

Sub Track

Colorectal Cancer–Advanced Disease

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr e15562)

DOI

10.1200/JCO.2021.39.15_suppl.e15562

Abstract #

e15562

Abstract Disclosures