Maurya, Priyanshi

e15713 Background: Fruquintinib demonstrated overall survival benefit in heavily pretreated metastatic colorectal cancer (mCRC) in FRESCO and FRESCO-2. The FDA approved fruquintinib on Nov 8, 2023 for adult patients with mCRC after standard chemotherapy plus anti-VEGF therapy, with anti-EGFR therapy when appropriate (e.g., RAS wild-type). Observed geographic variation in post-approval uptake suggests potential disparities in the delivery of evidence-based medicine across U.S. regions. Methods: We conducted a retrospective cohort study using Epic Cosmos, a database of over 300 million patient records from over 1,500 hospitals nationwide. We identified adults with metastatic colorectal cancer (mCRC) with prior standard systemic therapy exposure and recorded fruquintinib exposure following FDA approval beginning Nov 8, 2023. Fruquintinib uptake was analyzed by U.S. Census region and state, expressed as the proportion of eligible mCRC patients receiving fruquintinib within each geography. Results: Among 116,116 pre-treated mCRC patients, 6,722 (5.79%) had recorded fruquintinib exposure during the post-approval period. Uptake varied nearly five-fold across states (2.27%–11.33%) (Table). High-uptake states were disproportionately concentrated in the central U.S./Midwest, whereas multiple low-uptake states were observed in the West and Northeast, suggesting broader regional variation beyond state-to-state differences. Conclusions: In a large national EHR-derived cohort of pre-treated mCRC patients after U.S. approval, fruquintinib uptake demonstrated substantial geographic variation. These findings raise concern for inequities in delivery of evidence-based later-line therapy and highlight the need to identify modifiable system- and site-level drivers (e.g., access, referral patterns, treatment infrastructure) to promote equitable adoption. Fruquintinib uptake among eligible metastatic colorectal cancer patients by U.S. state. Rank Geography Eligible mCRC (N) Fruquintinib uptake (%) Overall Overall 116,116 5.79 Top 1 Oklahoma 1,236 11.33 2 Kansas 1,312 10.75 3 Indiana 2,448 10.70 4 Missouri 1,521 9.47 5 Connecticut 2,208 9.24 Bottom 1 Washington 1,232 2.27 2 Nevada 441 2.72 3 Rhode Island 476 2.73 4 Tennessee 1490 2.82 5 Maine 614 2.93 Fruquintinib uptake is reported as the proportion of eligible pre-treated metastatic colorectal cancer (mCRC) patients with recorded fruquintinib exposure following U.S. FDA approval. States are ranked by uptake percentage.

10576 Background: Type 2 diabetes mellitus (T2DM) and excess adiposity are independent risk factors for pancreatic cancer. Pancreatic cancer risk within T2DM across body-mass index (BMI) strata is heterogeneous in real-world cohorts and lean T2DM individuals may represent a distinct high risk phenotype. We compared pancreatic cancer incidence and post-diagnosis survival across BMI strata. Methods: We performed a retrospective comparative outcomes analysis using the TriNetX network. Adults with T2DM (HbA1c ≥6.5%) were categorized as obese (BMI ≥30 kg/m²) or lean (BMI <25 kg/m²). The lean cohort additionally excluded any patient with prior BMI of >25 kg/m² to control for cancer associated weight loss. The index event was first T2DM diagnosis, and outcomes were evaluated after a 365-day window. Patients with pancreatic cancer prior to the outcome window were excluded. Propensity score matching was done using the following parameters: age, sex, smoking status, pancreatitis, pancreatic cysts, chronic kidney disease, gallstones, family history of pancreatic cancer, and HbA1c. Outcomes assessed were incident pancreatic cancer over 10 years and all-cause mortality among patients with pancreatic cancer and T2DM. Results: Total number of patients in the obese group was 1,759,075 with mean age of 57 ± 13.4 years and in the lean cohort were 205,193 with a mean age of 61.8 ± 16.6 years. After propensity score matching, there were 204,086 patients in each group. Mean HbA1c levels were 7.4 ± 1.8% in the obese group and 7.9 ± 2.2% in the lean BMI group. The incidence of pancreatic cancer was 0.16% (n = 335) in obese patients as compared to 0.23% in lean (n = 478) patients with a risk difference of 0.07% (p <0.001). Obesity was associated with lower pancreatic cancer risk (RR 0.692, 95% CI 0.603–0.797; p < 0.001). In the subgroup analysis of patients diagnosed with pancreatic cancer, obese patients had longer median survival (1,109 vs 651 days) with HR 0.853 (95% CI 0.793 - 0.918; p <0.001). Conclusions: Lean adults with T2DM had a higher incidence of pancreatic cancer and worse post-diagnosis survival than obese patients. These results identify lean T2DM as a distinct high-risk phenotype and demonstrate that pancreatic cancer risk within T2DM is heterogeneous and not solely attributable to excess adiposity. Further investigation is needed to elucidate the biological mechanisms underlying this association and its implications for clinical risk assessment. Pancreatic cancer incidence and associated risk estimates among obese and lean adults with type 2 diabetes mellitus. Cohort Pancreatic cancer incidence RD RR Obese T2DM(n = 204,086) 0.16% (n = 335) 0.07% (95% CI: 0.04 - 0.10), p < 0.001 1.44 (95% CI: 1.25 - 1.66) Lean T2DM(n = 204,086) 0.23% (n = 478) Abbreviations: CI, confidence interval; RD, risk difference; RR, relative risk; T2DM, type 2 diabetes mellitus.