ImportanceProfessional society guidelines recommend treating patients with metastatic colorectal cancer with targeted therapies, including epithelial growth factor receptor (EGFR) inhibitors and vascular endothelial growth factor (VEGF) inhibitors, depending on the presence or absence of certain mutations. Since most studies of first-line targeted therapies have been limited by sample size, there is a need for larger studies using data from routine clinical care.ObjectivesTo identify factors associated with receipt of first-line targeted therapies among patients with metastatic colorectal cancer for whom RAS or BRAF mutation data in the tumor were available and investigate whether targeted therapy is associated with survival.Design, Setting, and ParticipantsThis cohort study used deidentified data from an electronic health record–derived database to include patients from 800 sites of patient care across the US who were diagnosed with de novo metastatic colorectal cancer between January 1, 2013, and March 31, 2020 (n = 9134).Main Outcomes and MeasuresReceipt of first-line targeted therapy, categorized as ever having received EGFR inhibitors, VEGF inhibitors, or neither. The secondary outcome was overall survival.ResultsThe study population included 9134 patients. The median age at diagnosis was 62 years (IQR, 53-71 years), 5019 (54.9%) were male, and 5692 (62.3%) were White. The median follow-up period was 15 months. Overall, 713 patients (7.8%) received EGFR inhibitors and 5081 patients (55.6%) received VEGF inhibitors as part of their first-line treatment. Among patients with RAS wild-type (RAS-WT) tumors, 625 patients (15.5%) received EGFR inhibitors and 2053 patients (50.9%) received VEGF inhibitors. In patients with RAS mutant (RAS-Mut) tumors, 50 patients (1.1%) received EGFR inhibitors and 2682 patients (59.7%) received VEGF inhibitors; among those with BRAF-mutant (BRAF-Mut) tumors, 38 patients (6.3%) received EGFR inhibitors and 346 patients (57.2%) received VEGF inhibitors. More than one-third of the patients (36.6%) received neither EGFR inhibitors nor VEGF inhibitors. Compared with patients younger than age 40 years, those aged 80 years or older had significantly lower odds to receive targeted therapies (EGFR or VEGF inhibitors in patients with RAS-WT tumors: adjusted odds ratio [aOR], 0.53; 95% CI, 0.36-0.79; and VEGF inhibitors in patients with RAS-Mut tumors: aOR, 0.62; 95% CI, 0.42-0.90). Improved survival was associated with EGFR inhibitor therapy in patients with RAS-WT tumors (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.74-0.98). Unlike in clinical trials, however, no survival benefit was noted with use of VEGF inhibitors among patients with RAS-WT (aHR, 1.00; 95% CI, 0.91-1.11) or RAS-Mut (aHR, 1.01; 95% CI, 0.93-1.10) tumors.Conclusions and RelevanceThe findings of this study showed mixed results on survival benefits associated with targeted therapy. In addition, given that some of the results differed from those of randomized clinical trials, this study highlights the importance of using data originating from routine clinical care.

Background Standard clinical practice and national guidelines dictate somatic testing of metastatic colorectal cancer (mCRC) tumors to guide appropriate therapy; however, previous studies suggest that not all patients are tested. The objective of this study was to investigate potential differences in testing for mCRC by demographic and clinical factors. Methods We performed a retrospective review of de‐identified patient data derived from electronic health records (EHRs) of 25,469 patients diagnosed with mCRC between the years 2013 and 2020. Our outcome was a receipt of the following tests: (a) biomarker testing (BRAF, KRAS, NRAS, MMR/MSI) and (b) next‐generation sequencing (NGS). We interrogated our data using the machine‐learning algorithm Classification and Regression Tree (CART), a unique approach to identifying combinations of, rather than individual demographic and clinical characteristics associated with receipt of testing. Results A total of 25,469 patients were identified with mCRC. Of these, 21,133 (83%) received either biomarker testing only (n = 12,485) or any testing (biomarker + NGS) (n = 8648). The proportion of patients who received any testing increased over calendar time for all age, race, and sex categories. Receipt of any testing was highest (90%) among younger and patients with better performance status, and there was no difference in receipt of any testing by race. The highest percentage of NGS testing was among those with better performance status, <70 years old, commercial or other governmental program payers, and low comorbidity burden; however, those who were Black or Hispanic had a lower prevalence of NGS testing than those who were White. Conclusions and Relevance Considerable variations exist in somatic biomarker testing across subgroups of the population. Identification of genomic alterations can aid in determining targeted treatment and improving clinical outcomes; therefore, equitable use of these testing strategies, particularly NGS, is necessary.

e15557 Background: Oncology has greatly benefited from the use of clinical genomics to aid diagnostic and treatment decisions. To inform targeted therapy, standard practice dictates molecular testing of metastatic colorectal cancer (mCRC) tumors through genomic testing (GT), including molecular biomarker, single gene, or next-generation sequencing (NGS). While persisting disparities in CRC screening, treatment, and outcomes have been well described, little is known about differences in GT for mCRC. Using all-payer electronic health record-derived de-identified data from a real-world database generated from routine clinical care across the U.S., we identified combinations of demographic and clinical characteristics, rather than individual factors, associated with GT. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. During the study period, the de-identified data originated from approximately 280 US cancer clinics (̃800 sites of care). Our study population included 26,524 patients with mCRC during the years 2013-2020. We evaluated documentation of receipt of GT (individual biomarker or NGS) measured within one year of diagnosis of metastatic disease, by demographic (age, sex, and race/ethnicity), payer type, de novo metastatic cancer (vs. progression to metastatic disease), tumor site (colon vs. rectum), Eastern Cooperative Oncology Group (ECOG) performance status, and year of diagnosis. We identified Elixhauser comorbid conditions from ICD codes, and grouped them by count (0-4, 5+). We conducted Classification and Regression Tree (CART) analysis, a machine learning approach to identify combinations of demographic and clinical characteristics associated with receipt of GT. Results: Nearly 83% had documented GT, 90% of whom did so within 6 months of diagnosis. The largest group of patients with GT at 90% consisted of individuals with colon cancer, 64 years of age or younger, 0-4 comorbidities, and an ECOG score of 0 or 1 (n = 2,004). Conversely, the lowest rates of GT ( < 60%) were observed among women 75 years of age or older, despite having 0-4 comorbidities (n = 1,314). In this group of patients, GT was higher among those with ECOG score of 1 than among those with high ECOG scores (66% and 54%, respectively). On the other hand, 71% of patients 75 years of age or older with 5+ comorbidities and high ECOG scores received GT. Conclusions: Considerable variations exist in GT across subgroups of the population. Additional analysis is warranted to characterize young and healthy patients who did not receive GT, and those who did get tested despite their older age and compromised health status. Future analyses will investigate whether documentation of receipt of GT is associated with treatment decisions and outcomes.

Background: Circadian disruption is a potential risk factor for advanced prostate cancer, and light at night (LAN) exposure may disrupt circadian rhythms. We evaluated whether outdoor LAN increases the risk of prostate cancer. Methods: We prospectively followed 49,148 participants in the Health Professionals Follow-up Study from 1986 through 2016. We estimated baseline and cumulative time-varying outdoor LAN with ~1 km2 resolution using data from the US Defense Meteorological Satellite Program’s Operational Linescan System, which was assigned to participants’ geocoded addresses. Participants reside in all 50 US states and reported a work or home address. We used multivariable Cox models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between outdoor LAN and risk of overall (7,175 cases) and fatal (915 cases) prostate cancer adjusting for individual and contextual factors. Results: There was no association between the interquartile range increase in cumulative LAN and total (HR:1.02, 95% CI 0.98, 1.06) or fatal (HR: 1.05, 95% CI: 0.96, 1.15) prostate cancer in adjusted models. However, there was a positive association between baseline LAN and total prostate cancer among non-movers (HR: 1.06, 95% CI:1.00,1.14) including among highly screened participants (HR: 1.11, 95% CI:1.01,1.23). Conclusions: There was a suggestive positive association between baseline outdoor LAN and total prostate cancer. Additional studies with different measures of outdoor LAN and in more diverse populations are necessary. Impact: To our knowledge, this is the first longitudinal cohort study exploring the relationship between outdoor LAN and prostate cancer.

<p>Supplementary Figure 1. Cubic splines to check for nonlinearity (A) Spline for total prostate cancer; (B) Spline for fatal prostate cancer</p>