Real-world analysis of biomarker testing and actionability in metastatic colorectal cancer (mCRC) in the United States (US).
Authors: Parikh Aparna Raj , Vieira Maria Cecilia , Rockey Michelle L. , Boyd Marley , Rava Andrew , Rau Reina , Kelton John M. , Abrahami Devin 
Published: October 2023

115 Background: BRAF, MSI-H, RAS and HER-2 are biomarkers recognized for their potential to inform prognosis and/or treatment decisions in mCRC. This study aims to estimate the impact of biomarker testing on treatment actionability in mCRC patients in the US. Methods: This was a retrospective cohort study in the Flatiron Health Database (2013-2022). Adults ≥18 years old with mCRC, ≥2 months of follow-up, and receipt of a biomarker test (result or specimen received date) for BRAF, MSI-H or RAS were included. Patients were excluded if they had no activity within 90 days after mCRC date or a death date recorded prior to mCRC date. For biomarker informed treatment actionability, patients were excluded if they received the following targeted therapies (BRAF: encorafenib+cetuximab) or immunotherapies (MSI-H: pembrolizumab, nivolumab, or ipilimumab) prior to positive biomarker result. Time from mCRC diagnosis to first test result, first test result to diagnosis of mCRC, and proportion of mCRC patients tested per year were reported. For actionability, the proportion of BRAF or MSI-H patients receiving actionable treatments listed above, and proportion of RAS patients receiving potentially inappropriate treatment (panitumumab, cetuximab) were also assessed. The start of the study period for the actionability analysis was adjusted to when these therapies were FDA approved (BRAF: 04/2020; MSI-H: 11/2015). Results: 26,120 patients were included. Median (Q1, Q3) time from mCRC diagnosis to first biomarker result was 28 (9, 75) days and median (Q1, Q3) time from first biomarker result to mCRC diagnosis was 439 (219, 752) days. Testing rates increased from 2013-2022 for each biomarker: BRAF (11.5-78.8%), MSI/MMR (15.4-84.4%), KRAS (42.1-79.1%), and NRAS (3.8-75.3%). 74 (16.2%) BRAF patients received FDA approved targeted therapy; 39 as their first recorded regimen in flatiron. Receipt of actionable targeted therapies for BRAF mutations was consistent (~17%) in the first-year post-approval compared with the most recent year of data. 535 (58.3%) MSI-H patients received biomarker informed immunotherapy; 351 as their first recorded regimen. The proportion of MSI-H patients receiving immunotherapy increased from 50.6% in the first-year post-approval to 67.4% in the most recent year. Potentially inappropriate treatment was identified in 266 (2.6%) RAS patients; 3.2% in the first year of the study period compared with 1.3% in 2022. Conclusions: Current real-world biomarker testing rates reflect increased adoption of clinical guideline recommendations, leading to improved treatment actionability as shown by sustained administration of targeted therapies (BRAF), increased administration of immunotherapy (MSI-H), and less frequent use of potentially inappropriate treatments (RAS). Further improvements in testing and receipt of appropriate therapies may lead to better patient outcomes.