Study shows disparities in access to molecular diagnostics for colorectal cancer
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Although testing for microsatellite instability and mismatch repair deficiency has increased for advanced colorectal cancer, substantial gaps in testing remain among certain patient groups, according to study results.
The results, presented at American Association for Cancer Research Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, showed testing occurred less frequently among older patients, those in historically underrepresented groups, and among uninsured or Medicaid-insured patients.
“The development of molecular diagnostics has helped to transform modern oncology, with the number of new FDA-approved molecularly targeted therapies growing each month. For example, detection of high DNA microsatellite instability [MSI] and mismatch repair deficiency [MMR] has become an important indication for use of immune checkpoint inhibitors in patients with advanced colorectal cancer,” Julian Bryan Iorgulescu, MD, FACP, instructor in the department of pathology at Brigham and Women’s Hospital, told Healio. “However, although there has been a lot of recent health services research on the disparities that cancer patients face in accessing standard-of-care therapies, there has been comparably very little research into whether there are disparities in access to molecular diagnostic testing.”
Investigators used the National Cancer Database to pool data on 45,326 patients newly diagnosed with histopathologically confirmed advanced colorectal cancer between 2010 and 2016. Patients who lacked data about MSI and MMR testing or who were initially diagnosed at another institution were excluded.
Receiving MSI and MMR testing via immunohistochemistry or molecular diagnostic served as primary endpoints.
Researchers used multivariable logistic regression to evaluate the association between MSI and MMR testing and patient demographic, socioeconomic and care setting characteristics, as well as with receipt of immunotherapy.
Results showed 26.5% of patients (n= 11,998) underwent MSI and MMR testing. The rates of testing increased from 14.4% in 2010 to 41.1% in 2016 (adjusted OR per year = 1.26; 95% CI, 1.25-1.29).
Older age was significantly associated with a lower likelihood to undergo testing (age 70-79 years vs. 60-69 years, adjusted OR [aOR] = 0.83; 95% CI, 0.77-0.89; age 50-59 years, aOR = 1.25; 95% CI, 1.16-1.33). Testing also appeared less common among men (aOR = 0.94; 95% CI, 0.9-0.99) and Blacks compared with whites (aOR = 0.87; 95% CI, 0.82-0.94).
Moreover, testing was less common among patients who were uninsured (aOR = 0.78; 95% CI, 0.7-0.86), Medicaid-insured (aOR = 0.87; 95% CI, 0.8-0.94) and Medicare-insured (aOR = 0.87; 95% CI, 0.81-0.93) compared with privately insured, as well as among those diagnosed at a community (aOR = 0.6; 95% CI, 0.56-0.66) or comprehensive community cancer program (aOR = 0.76; 95% CI, 0.72-0.8) compared with those diagnosed at an academic or NCI comprehensive cancer program.
Of note, among patients diagnosed in 2016, those who were not tested also were less likely to receive immunotherapy (aOR = 0.61; 95% CI, 0.53-0.68).
“The magnitudes of some of the gaps in guideline-recommended MSI and MMR testing were quite surprising to us, but we are finding that many of the same socioeconomic factors associated with disparities in patients’ access to treatment and high-quality care are also associated with disparities in access to molecular testing,” Iorgulescu said.
“National cancer databases, like the one we used for our research, have been indispensable resources for identifying many of the disparities in health care for cancer patients,” Iorgulescu added. “Still, much more research is needed to convert what we are learning from national data into effective strategies for reducing those disparities. For our projects, that means finding ways to improve cancer patients’ access to critical molecular diagnostics.”
Perspective
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Biomarkers in colorectal cancer have ushered in a new era of therapeutic targets and prognostic significance for a disease that is the third-leading cause of cancer-related death in the United States.
MMR deficiency is characteristically found in Lynch syndrome but also has been observed in 15% of all colorectal cancers and leads to high rates of MSI mutations. Historically, MSI and MMR testing was recommended for patients aged younger than 50 years with a history of colorectal cancer due to increased incidence of Lynch syndrome. In 2017, the National Comprehensive Cancer Network (NCCN) guidelines expanded testing recommendations for MSI and MMR to all patients with newly diagnosed colorectal cancer.
Until recently, MSI and MMR testing in colorectal cancer largely carried prognostic implications, with MSI-high tumors more frequently occurring in the right colon and carrying a better prognosis. Current NCCN recommendations for stage IV colorectal cancer include pembrolizumab (Keytruda, Merck), nivolumab (Opdivo, Bristol Myers Squibb), or nivolumab plus ipilimumab (Yervoy, Bristol Myers Squibb) as treatment options for patients with deficient MMR or MSI-high status. One of the most significant trials to be presented at this year’s ASCO20 Virtual Scientific Program was KEYNOTE-177, which showed pembrolizumab to have more than double the median PFS compared with conventional chemotherapy for MSI-high advanced colorectal cancer, leading to FDA approval in the first-line setting in June. However, despite these advances, disparities in MSI and MMR testing rates persist throughout the U.S.
This study by Iorgulescu and colleagues builds upon work done by researchers at Fox Chase Cancer Center who also accessed the National Cancer Database to look at rates of MSI and MMR testing in all newly diagnosed colorectal cancer from 2010 through 2012 and found only 28.2% received testing.
In the Fox Chase Cancer Center study, older age, Black race, lack of insurance or Medicare/Medicaid coverage, nonacademic or research facility care, and stage IV disease were all found to be independently associated with not receiving MMR tissue testing.
Because NCCN guidelines did not recommend universal MMR testing in colorectal cancer until 2017, the low rates of MSI and MMR testing from 2010 to 2016 in the current study are expected, especially among older individuals, as historical guidelines only recommended testing for those aged younger than 50 years. However, the independent associations of race, insurance coverage and care center with lack of MSI and MMR testing also point to inherent structural barriers to biomarker testing that oncologists and policymakers must address to ensure equitable access to biomarker testing, especially with the emergence of immune checkpoint inhibitors in colorectal cancer. The authors of the current study are to be commended for highlighting an important potential disparity contributing to heterogeneity in colorectal cancer outcomes —increasing awareness may result in closing these gaps.
References:
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Shaikh T, et al. JAMA Oncol. 2018;doi:10.1001/jamaoncol.2017.3580.
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Iorgulescu JB, et al. Abstract PO-091. Presented at: American Association for Cancer Research Virtual Meeting: The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Oct. 2-4, 2020.
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