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63 Microsatellite instability/mismatch repair biomarker testing disparities in patients with advanced colorectal cancer: Implications for immune checkpoint inhibitors
  1. Bryan Iorgulescu
  1. Dana-Farber Cancer Institute, Boston, MA, USA


Background Immune checkpoint inhibitors have revolutionized outcomes for patients with a spectrum of cancer types, including the first tissue/site-agnostic FDA approvals (in 2017 for 2nd-line and 2020 for 1st-line) for advanced cancers with DNA microsatellite instability-high/mismatch repair deficiency (MSI-High/MMRd). However, the factors associated with patients‘ access to MSI/MMR testing are unknown.

Methods Patients ≥20-years-old who newly presented with histopathologically-confirmed stage 4 colorectal adenocarcinoma from 2010–2016 were identified from the National Cancer Database, which comprises >70% of all newly-diagnosed cancer patients in the U.S. Patients were excluded if they lacked data about MSI/MMR testing or were initially diagnosed at another institution. The primary outcome was receiving MSI/MMR testing, either via immunohistochemistry or molecular diagnostic. Patient demographic, socioeconomic, and care setting characteristics were evaluated for association with MSI/MMR testing, as well as between MSI/MMR testing and immunotherapy receipt, using multivariable logistic regression.

Results Of 45,326 newly-diagnosed stage 4 colorectal adenocarcinoma patients, only 26.5% (n=11,998) received MSI/MMR testing – rising from 14.4% in 2010 to 41.1% in 2016 (adjusted odds ratio [aOR] 1.26/year, 95% confidence interval [95%CI] 1.25–1.29, p<0.001). Overall, patients who were older (referent 60–69-years-old; 70–79-years-old aOR 0.83, 95%CI: 0.77–0.89, p<0.001; 50–59-years-old aOR 1.25, 95%CI: 1.16–1.33, p<0.001), male (aOR 0.94, 95%CI: 0.90–0.99, p=0.01), or of Black non-Hispanic race/ethnicity (aOR 0.87 vs. White non-Hispanic, 95%CI: 0.82–0.94, p<0.001) were independently less likely to receive testing.Additionally, patients who were either uninsured (referent private insurance, aOR 0.78, 95%CI: 0.70–0.86, p<0.001), Medicaid-insured (aOR 0.87, 95%CI: 0.80–0.94, p=0.001), or Medicare-insured (aOR 0.87, 95%CI: 0.81–0.93, p<0.001); or diagnosed at community (referent academic/NCI-comprehensive cancer program, aOR 0.60, 95%CI: 0.56–0.66, p<0.001) or comprehensive community (aOR 0.76, 95%CI: 0.72–0.80, p<0.001) cancer programs, were also significantly less likely to be tested. Even for patients diagnosed in 2016, untested patients received independently less immunotherapy than tested patients (aOR 0.61, 95%CI: 0.53–0.68, p<0.001).

Conclusions MSI/MMR testing rates for stage 4 colorectal cancer patients have dramatically improved in recent years, but appeared underutilized in patients that were older, of Black non-Hispanic race/ethnicity, uninsured or Medicaid-insured, or diagnosed at community programs. Our findings suggest that socioeconomic and care setting opportunities exist for improving access to testing of this important predictive biomarker for immune checkpoint blockade.

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