Real-world rates of FDA-approved targeted therapy and immunotherapy prescriptions for patients with metastatic colorectal cancer in the VA’s National Precision Oncology Program (NPOP).
Authors: Nono Djotsa Alice , Winski David , Nguyen Theresa Hoang-Anh , Ahmed Sara , Strickler John H , Becker Daniel Jacob , Vashistha Vishal , Kelley Michael J. 
Published: June 2023

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Background: Colorectal cancer is the fourth most common cancer among Veterans and the third leading cause of cancer-related death in the USA. Use of comprehensive genomic profiling (CGP) to guide administration of FDA-approved biomarker directed therapies can improve outcomes among metastatic CRC (mCRC) patients. We sought to compute the rates of actionable biomarkers and prescriptions of associated FDA-approved therapies among Veterans in NPOP. Methods: The NPOP database was queried to identify mCRC patients who had undergone CGP via tissue or liquid biopsy between February 2019 and July 2022 and had one of the following 5 actionable biomarker profiles: NRAS/ KRAS/ BRAF wildtype, BRAF V600E, MSI-H, TMB-H, or NTRK fusion or rearrangement. The VA’s Corporate Data Warehouse (CDW) was queried to extract prescription data for seven FDA-approved biomarker-directed therapies (targeted agents and immune checkpoint inhibitors (ICIs)). Rates of CGP-directed therapy prescriptions were assessed based upon biomarker and patient characteristics (sex, race, ethnicity, and rurality). Results: A total of 908 mCRC patients underwent CGP, with 81.4% bearing colon adenocarcinoma (COAD) and 18.6% rectal adenocarcinoma (READ). Rates of actionable biomarkers associated with FDA-approved therapies were as follows: NRAS/ KRAS/ BRAF wildtype (34.4%), TMB-H (9.6%), BRAF V600E (7.7%), MSI-H (5.6%), TMB-H and MSI-H (5.6%), and NTRK Fusion or rearrangement (0.3%). The combined rates of any actionable variant were 47.4% for COAD and 44.4% for READ patients. Relative to patients without actionable biomarkers, patients with BRAF V600E mutations were more likely to be older and white; patients with NRAS/ KRAS/ BRAF wildtype were more likely to be younger (all p < 0.001). Among the 424 eligible patients, the frequencies of FDA-approved CGP-directed therapy prescriptions were as follows: MSI-H (70.7%), TMB-H (47.4%), NRAS/ KRAS/ BRAF wildtype (38.5%), and BRAF V600E (17.1%). Across all included biomarkers, African Americans (53.4%) were more likely to receive these therapies than whites (36.8%); and patients with prescriptions were more likely to be younger that those without (all p < 0.01). Conclusions: Nearly 30% of patients with MSI-H mCRC did not receive efficacious ICIs, and though disease laterality data was not readily available, a substantial number of eligible patients also did not receive EGFR inhibitors. This underuse of EGFR inhibitors has been reported previously [1].There were racial and age differences in prescription rates. Further studies should evaluate the barriers to prescribing CGP-directed therapies in the care of mCRC patients. Keywords: molecular testing, metastatic colorectal cancer, comprehensive genomic profiling, actionable biomarkers, FDA approved therapies, veterans. [1] Becker et al. 2021 PMID 34250412.