Assessing Oncologists’ Adoption of Biomarker Testing in Metastatic Colorectal Cancer Using Real-World Data

Abstract

Background Despite national guideline recommendations for universal biomarker testing (KRAS, NRAS, BRAF, and mismatch repair/microsatellite instability [MMR/MSI]) in all patients with metastatic colorectal cancer (mCRC), little is known regarding adherence to these recommendations in routine practice. Methods We retrospectively reviewed patients with mCRC diagnosed between 1/1/2013-12/27/18 from a de-identified electronic health record (EHR)-derived database. We analyzed disparities in KRAS, NRAS, BRAF, and MMR/MSI testing by race, age, gender, and insurance status using Chi-Square tests and T-tests. We evaluated changes in biomarker testing over time with attention to changes around dates of landmark publications and guideline updates using Chi-square tests and Cochran-Armitage tests. Results A total of 20,333 patients were identified of which 66.6% had test results for any biomarker. Rates of test results for all four biomarkers significantly increased over time (p < 0.001). However, as of 6/30/2018 the rate of test results was only 46% for NRAS, 56% for KRAS, and 46% for BRAF. As of 12/31/2017 rate of MMR/MSI testing was 59%. Higher documented testing rates were associated with younger age, lower ECOG performance status, and commercial insurance. There were no clinically meaningful and/or statistically significant differences in documented testing rates by tumor sidedness, race, gender, or initial stage. Conclusions Increased rates of documented testing for NRAS, BRAF and MMR/MSI in mCRC was seen between 2013-2018 reflecting adoption of guideline recommendations. However, the rate of documented testing remains lower than expected, and warrants additional research to understand the extent to which this may represent a clinical practice quality concern.

A registry-based study on universal screening for defective mismatch repair in colorectal cancer in Denmark highlights disparities in screening uptake and counselling referrals

“…Complete diagnostic test strategies linked to high uptake of genetic testing have been demonstrated to be an efficient and cost-effective way to detect Lynch syndrome with the cause of the MMR defect explained in 9 out of 10 patients [ 3 , 9 , 38 , 39 ]. At the same time, suboptimal rates of genetic counselling and genetic testing have been documented with 41–55% complete evaluation rates in studies from e.g., the US, Ireland, Canada, Australia, and Korea [ 22 , [40] , [41] , [42] , [43] ]. In our series, uptake of genetic counselling and/or germline genetic diagnostics was 20%, ranging from 11·7% in the MLH1 group to 58·2% in the MSH2 group.…”

Response to osimertinib in a colorectal cancer patient with an EGFR T790M mutation: A case report

“…However, guidelines currently recommend testing for only a limited set of genes, including NRAS, KRAS, BRAF V600E, and mismatch repair/ microsatellite instability, with consideration to test for HER2 amplifications and NTRK fusions in the refractory disease setting[ 9 ]. A retrospective review of 23 US-based oncology practices demonstrates that even these limited gene panels are underutilized; only 40% of patients underwent guideline-recommended genomic testing for any of these genomic markers, a rate that has not increased since 2013[ 13 , 14 ].…”

Multi-Omics Approaches in Colorectal Cancer Screening and Diagnosis, Recent Updates and Future Perspectives

“…At present, for patients with mCRC, it is recommended to determine KRAS/NRAS and BRAF mutation status, as well as HER2 amplification and microsatellite instability high (MSI)/mismatch repair (MMR) status (if not performed already) [ 4 ]. Recent studies have demonstrated that immune checkpoint inhibitor therapy is effective in treating dMMR/MSI-H mCRC tumours at advanced stages of the disease [ 5 ]. The discovery of new molecular biomarkers in CRC and other cancers has begun to follow the approval of tumour-agnostic drugs, including NTRK1-3 translocations and high tumour mutational burdens (TMBs) [ 6 , 7 ].…”