1. Froelich, Warren

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Although the use of a key biomarker to assess treatment options for patients with advanced colorectal cancer has increased in recent years, significant gaps in testing remain for some, according to a new study from the Brigham and Women's Hospital in Boston.

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These microsatellite instability and mismatch repair deficiency (MSI/MMR) tests are now used as a treatment guideline to determine which patients might best respond to immunotherapeutic options that recently have improved outcomes in a cross section of cancer types. But testing gaps remain for certain patients based on race and ethnicity, insurance types, age, and hospital settings.


"Taken together, our findings suggest that both socioeconomic and care-setting opportunities exist for improving access to testing of this important biomarker," said J. Bryan Iorgulescu, MD, FCAP, Instructor in Pathology at Brigham and Women's Hospital, who presented these findings at the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held by the American Association for Cancer Research (AACR).


Generally, the MSI/MMR status of a patient is determined after a tumor is surgically removed. Those with MSI-H (high genetic instabilities) suggest that genes that regulate DNA (MMR) aren't working the way they should. Such instabilities are found in about 15 percent of all tumors in patients with advanced stage IV colorectal cancer.


By contrast, approximately 80-85 percent of advanced colorectal cancers are classified as MSS, whose tumors are sometimes referred to as "cold." Most non-MSI tumors exist in an environment that suppresses the immune system and thus do not respond well to immunotherapies.


"Certain immune checkpoint inhibitors have revolutionized outcomes for patients with a growing selection of cancer types, including the first site agnostic FDA approval for treatment of any MSI-H/MMR deficiency that's cancerous, and most recently the first-line setting for MSI-H/MMR for advanced colorectal cancer," said Iorgulescu.


On June 29, 2020, the FDA approved pembrolizumab as a single-agent, first-line treatment for patients with unresectable or metastatic colorectal cancer. The drug, an immunotherapy, doubled progression-free survival in MSI-H colorectal cancer patients from 8.2 months for standard-of-care chemotherapy to 16.5 months.


The National Comprehensive Cancer Network guidelines recommend MSI/MMR testing for all newly diagnosed cancer colorectal cancer patients. However, factors associated with patient access to this test have remained unknown.


Study Details

To address this question, Iorgulescu and colleagues undertook a retrospective analysis of the National Cancer Database, which comprises more than 70 percent of all newly diagnosed cancer patients in the United States. The researchers identified adult patients (aged 20 years or more) with newly diagnosed stage IV colorectal adenocarcinoma between the years 2010 and 2016 who had complete data about MSI/MMR testing. Patients who lacked data about MSI and MMR testing, or who were initially diagnosed at another institution, were excluded.


The researchers then used multivariable logistic regression to evaluate the association between MSI and MMR testing and patient demographics, including socioeconomic and care setting factors.


Of the 45,326 newly diagnosed stage IV colorectal adenocarcinoma patients in the study, only 26.5 percent received MSI/MMR testing from 2010 to 2016, though utilization increased from about 14.4 percent in 2010 to 41.1 percent in 2016.


The study found that patients who were older and Black non-Hispanic were less likely to be tested. About 41 percent of White, non-Hispanic patients were tested in 2016, compared to 39 percent Black, non-Hispanic patients. About 64 percent of younger patients age 20-29 were tested, compared to 30 percent for those 80 and older.


Tracking insurance, the study found that 36 percent of Medicare patients were tested in 2016; 38 percent with no insurance; 45 percent on Medicaid; and 47 percent with private insurance.


"Prior to 2017, the National Comprehensive Cancer Network guidelines only recommended testing for colorectal cancer patients younger than 50, so the lower rates of testing among older patients and Medicare-insured patients from 2010 to 2016 weren't wholly unexpected," Iorgulescu said in an interview.


For clinical care settings, the study found that 30 percent of patients with advanced colorectal cancer treated in community hospitals were tested for the biomarker; 38 percent in comprehensive community care hospitals; 42 percent in an integrated network; and 50 percent in academic/NCI-designated hospitals.


"The extent of the gaps in MSI/MMR testing by patients' insurance coverage (or lack thereof) and hospital type were quite surprising to us," Iorgulescu stated. "But we're finding that many of the same socioeconomic and care-setting disparities in patient access to high-quality cancer care are also associated with disparities in access to molecular biomarker testing."


Iorgulescu said that a key next step is identifying the drivers of these disparities and to begin to develop solutions to close the gaps in access to MSI/MMR testing for patients with advanced colorectal cancer.


"For the overall field, moving forward, ensuring that National Cancer Database keeps pace with the advances in precision oncology and collect clinically relevant molecular testing data will be crucial," he added. "Other initiatives, like the National Cancer Institute's National Survey of Precision Medicine in Cancer Treatment, will also play critical roles in helping us better understand barriers to molecular testing."


Warren Froelich is a contributing writer.