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Andrew Trunk, Matthew Braithwaite, Christopher Nevala-Plagemann, Lisa Pappas, Benjamin Haaland, and Ignacio Garrido-Laguna

Background: BRAF mutations portend a poor prognosis in metastatic colorectal cancer (mCRC). Whether these patients may benefit from more aggressive frontline chemotherapy with a triplet regimen such as FOLFOXIRI remains unclear. We used real-world data from a cohort of patients in the United States to assess the BRAF testing rate, determine the prevalence of FOLFOXIRI use, and compare survival outcomes in mCRC, stratified by BRAF mutation status and first-line therapy. Methods: A nationwide electronic health record–derived deidentified database was reviewed for patients diagnosed with mCRC between 2013 and 2018. Those with documented BRAF mutation testing who received standard first-line therapy were included. Kaplan-Meier estimates with corresponding log-rank tests and Cox proportional hazards modeling compared survival outcomes stratified by BRAF status and first-line therapy. Results: Of 4,457 included patients, 3,991 (89.5%) had BRAF wild-type (BRAFwt) and 466 (10.5%) had BRAF-mutated (BRAFmt) mCRC. Median overall survival (OS) was 15.4 months in the BRAFmt group versus 28.1 months in the BRAFwt group (hazard ratio [HR], 0.48; 95% CI, 0.41–0.56; P<.001). Only 3% of patients with BRAF mutations received first-line FOLFOXIRI ± bevacizumab, with a median OS of 13.8 months compared with 15.5 months in those treated with doublet chemotherapy ± bevacizumab (P=.38). In patients with BRAF mutations, propensity-weighted analysis did not detect a significant improvement in OS with FOLFIRI + bevacizumab (HR, 0.90; 95% CI, 0.58–1.39; P=.63) or FOLFOX/CAPEOX + bevacizumab (HR, 0.81; 95% CI, 0.52–1.26; P=.35) versus doublet chemotherapy alone. In 2018, only 56% of patients diagnosed with mCRC had documented BRAF testing at any time. Conclusions: This real-world data analysis confirms the negative prognostic impact of BRAF mutations in mCRC and suggests that FOLFOXIRI has not been widely adopted in the United States. The proportion of patients with documented BRAF testing in this real-world population was low at 56%. We were unable to show any significant difference in OS of patients with BRAFmt mCRC based on the first-line therapy received.

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Christopher Nevala-Plagemann, Siddharth Iyengar, Andrew D. Trunk, Lisa Pappas, Benjamin Haaland, and Ignacio Garrido-Laguna

Background: Post hoc analysis of the CALGB/SWOG 80405 trial suggests that anti-EGFR therapy may be superior to bevacizumab when added to first-line chemotherapy in patients with metastatic colorectal cancer (mCRC) who have left-sided primary tumors. We evaluated trends in use of anti-EGFR agents in patients with left-sided RAS/RAF wild-type (WT) mCRC and compared clinical outcomes among the most commonly used treatment strategies. Methods: A nationwide electronic health record (EHR)–derived deidentified database was reviewed for patients with left-sided RAS/RAF WT mCRC. Treatment trends over time were assessed by fitting a linear model to the percentage of patients receiving anti-EGFR therapy. A propensity score weighted Cox model was used to compare overall survival (OS) stratified by first-line targeted therapy received. Results: A total of 1,607 patients with left-sided RAS/RAF WT mCRC received standard first-line chemotherapy. Of these, 965 (60%) received bevacizumab and 186 (12%) received an anti-EGFR agent. The percentage of patients receiving an anti-EGFR increased from 9% in 2013 to 16% in 2018. Median OS for patients treated with chemotherapy alone was 27.3 months (95% CI, 24.8–32.3), 27.5 months with bevacizumab (95% CI, 25.8–28.9; hazard ratio [HR], 0.88; P=.33), and 42.9 months with an anti-EGFR agent (95% CI, 36.0 to not reached; HR, 0.52; P=.005). Conclusions: This analysis suggests that chemotherapy with bevacizumab remained the most widely used first-line treatment strategy for patients with left-sided RAS/RAF WT mCRC in the United States in 2018. Despite this preference, treatment with an anti-EGFR agent was associated with improved OS.

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Kristen Kelley, Audrey York, Benjamin Haaland, Xuechen Wang, Shiven Patel, Adriana Coletta, and Christos Vaklavas

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Dominik J. Ose, Richard Viskochil, Andreana N. Holowatyj, Mikaela Larson, Dalton Wilson, William A. Dunson Jr, Vikrant G. Deshmukh, J. Ryan Butcher, Belinda R. Taylor, Kim Svoboda, Jennifer Leiser, Benjamin Tingey, Benjamin Haaland, David W. Wetter, Simon J. Fisher, Mia Hashibe, and Cornelia M. Ulrich

Background: This study aimed to understand the prevalence of prediabetes (preDM) and diabetes mellitus (DM) in patients with cancer overall and by tumor site, cancer treatment, and time point in the cancer continuum. Methods: This cohort study was conducted at Huntsman Cancer Institute at the University of Utah. Patients with a first primary invasive cancer enrolled in the Total Cancer Care protocol between July 2016 and July 2018 were eligible. Prevalence of preDM and DM was based on ICD code, laboratory tests for hemoglobin A1c, fasting plasma glucose, nonfasting blood glucose, or insulin prescription. Results: The final cohort comprised 3,512 patients with cancer, with a mean age of 57.8 years at cancer diagnosis. Of all patients, 49.1% (n=1,724) were female. At cancer diagnosis, the prevalence of preDM and DM was 6.0% (95% CI, 5.3%–6.8%) and 12.2% (95% CI, 11.2%–13.3%), respectively. One year after diagnosis the prevalence was 16.6% (95% CI, 15.4%–17.9%) and 25.0% (95% CI, 23.6%–26.4%), respectively. At the end of the observation period, the prevalence of preDM and DM was 21.2% (95% CI, 19.9%–22.6%) and 32.6% (95% CI, 31.1%–34.2%), respectively. Patients with myeloma (39.2%; 95% CI, 32.6%–46.2%) had the highest prevalence of preDM, and those with pancreatic cancer had the highest prevalence of DM (65.1%; 95% CI, 57.0%–72.3%). Patients who underwent chemotherapy, radiotherapy, or immunotherapy had a higher prevalence of preDM and DM compared with those who did not undergo these therapies. Conclusions: Every second patient with cancer experiences preDM or DM. It is essential to foster interprofessional collaboration and to develop evidence-based practice guidelines. A better understanding of the impact of cancer treatment on the development of preDM and DM remains critical.