583 Background: Optimal first-line biliary drainage for malignant biliary obstruction (MBO) remains debated. Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous biliary drainage (PBD) are both used, sometimes sequentially within the same admission. Comparative in-hospital effectiveness across real-world strategies is unclear. Methods: We analyzed 2020–2022 NIS adults hospitalized with malignant biliary obstruction who underwent ERCP and/or percutaneous biliary drainage, classifying the index strategy as ERCP-only, PBD-only, ERCP-first, or PBD-first. To address confounding by indication, we estimated multinomial propensity scores. Effects were estimated with survey-weighted marginal structural models. Results: Among 11,133 discharges (weighted ≈55,645), initial strategies were ERCP-only 91.2%, PBD-only 7.5%, ERCP-first 1.05%, and PBD-first 0.33%. After inverse-probability weighting, baseline covariates were balanced across strategies. Compared with ERCP-first, ERCP-only had lower in-hospital mortality (adjusted risk 3.10% vs 10.8%; aOR 0.26, 95% CI 0.14–0.49). PBD-only (aOR 0.83, 95% CI 0.43–1.61) and PBD-first (aOR 0.66, 95% CI 0.17–2.61) did not differ significantly from ERCP-first. ERCP-only was also associated with shorter length of stay (IRR 0.46, 95% CI 0.41–0.52) and lower total charges (cost ratio 0.54, 95% CI 0.47–0.61); PBD-only showed intermediate reductions (LOS IRR 0.77, 95% CI 0.68–0.88; cost ratio 0.75, 95% CI 0.65–0.86). Conclusions: ERCP-only initial strategy for MBO was associated with lower in-hospital mortality and reduced resource use compared with an ERCP-first combined approach. These findings support prioritizing definitive endoscopic drainage when feasible and may inform practice and trial design. In-hospital outcomes by initial biliary drainage strategy for malignant biliary obstruction (NIS 2020–2022). Strategy (index admission) Weighted share, % Mortality — aOR vs ERCP-first (95% CI) LOS — IRR vs ERCP-first (95% CI) Total charges — Cost ratio vs ERCP-first (95% CI) ERCP-only 91.2 0.26 (0.14–0.49) 0.46 (0.41–0.52) 0.54 (0.47–0.61) PBD-only 7.5 0.83 (0.43–1.61) 0.77 (0.68–0.88) 0.75 (0.65–0.86) ERCP-first (reference) 1.05 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) Models are survey-weighted marginal structural models with stabilized IPTW multiplied by NIS discharge weights; hospitals as PSUs and NIS strata applied. Mortality modeled with logistic regression (aORs); LOS with Poisson log link (IRRs); charges with gamma log link (cost ratios). Adjusted risks (mortality): ERCP-only 3.10% vs ERCP-first 10.8% (risk difference −7.7 percentage points; 95% CI −13.5 to −1.9).PBD-first represented 0.33% of discharges; estimates were imprecise and are omitted here for clarity (mortality aOR vs ERCP-first 0.66, 95% CI 0.17–2.61); sensitivity analyses excluding PBD-first yielded similar results.

42 Background: Early-onset colorectal cancer (EOCRC), defined as a diagnosis of colorectal cancer in a patient <50 years old, has been steadily increasing in incidence in resource-rich nations. It tends to be diagnosed at advanced stages, reinforcing the importance of timely diagnosis. Objectives: To describe the barriers to timely diagnosis of early-onset colorectal cancer. Methods: We performed a systematic review according to PRISMA guidelines, searching MEDLINE and Embase. Screening was done by two reviewers. Studies on experiences of patients with EOCRC and/or their caregivers or physicians were included. Case reports and literature reviews were excluded. A qualitative/thematic analysis was performed. Results: 14 studies with 4439 participants from the USA, Canada, Oceania, and Europe were selected for thematic analysis; they consisted of 6 surveys, 5 interviews, and 3 thematic analyses of internet forum posts. Patients and caregivers named misdiagnoses (11 studies), dismissive attitudes from physicians (8 studies), and lack of patient awareness of red flag symptoms (8 studies) as major factors delaying EOCRC diagnosis. The most common misdiagnosis was hemorrhoids (6 studies). Younger age (9 studies), female sex (3 studies) and non-specific symptoms (1 study) contributed to dismissal of patient concerns. None of the studies discussed lack of access to primary care as a factor. Patients reported having to self-advocate (6 studies) and see multiple physicians (5 studies) before their diagnosis with EOCRC. Conclusions: Given the rising incidence of advanced-stage EOCRC, it is imperative that physicians seriously consider possible malignancy in symptomatic patients <50 years old to allow timely diagnosis and treatment. Increased awareness of EOCRC has led to a lowered colon cancer screening age starting at 45 years old by The US Preventive Services Task Force. However, the starting age for colon cancer screening in Canada remains at 50 years old.

456 Background: Incidental gastrointestinal stromal tumors (GISTs) are increasingly recognized during bariatric surgery. The true frequency in sleeve gastrectomy (LSG) and how to manage lesions without derailing the bariatric plan remain practical questions. Methods: Single-center retrospective cohort of consecutive LSG specimens (2019–2023). We prespecified an intra-operative decision rule: systematic gastric inspection; no biopsy/aspiration; proceed to negative-margin wedge only if it does not materially alter the bariatric plan; if alteration is required, modify/convert only with prior consent and MDT agreement; otherwise defer and stage resection. A uniform pathology protocol (CD117/CD34/DOG1, mitotic index, necrosis) was applied. Incidence was estimated with 95% CIs. Results: Among 1,200 LSG specimens, 19 incidental gastric GISTs were identified (1.58%; 95% CI 1.02–2.46). All were unifocal micro-GISTs (0.2–0.6 cm), spindle-predominant, with non-significant mitoses and no necrosis. Immunohistochemistry was uniformly CD117/CD34/DOG1 positive. R0 resection was achieved within the sleeve specimen or with a simple wedge, without material change to the bariatric plan and without intra-operative biopsy/aspiration. Conclusions: In a high-volume bariatric surgical program, incidental micro-GISTs possess significant clinical implications yet can be effectively managed through negative-margin resection incorporated into LSG, while concurrently avoiding intra-operative biopsy or aspiration procedures that may pose a risk of tumor rupture and necessitate escalation to imatinib therapy. We advocate for a practice-oriented workflow (systematic intra-operative assessment → evaluation of resectability and impact triage → execution of wedge resection with an anticipated sleeve versus modification of the surgical plan with prior informed consent versus a decision to abort the procedure for collaborative decision-making), which is in alignment with current evidence and can be promptly implemented across various bariatric surgical pathways. Cohort summary (incidental micro-GISTs in LSG). Variable Value Total LSG specimens 1,200 Incidental GISTs (n) 19 Incidence (%, 95% CI) 1.58 (1.02–2.46) Tumor size, cm (range; mean ± SD) 0.2–0.6; ~0.41 ± 0.14 Histology Spindle predominant; occasional mixed Mitotic index Non-significant Necrosis Absent IHC CD117+, CD34+, DOG1+ (100%) Change in bariatric plan None material Intra-op biopsy/aspiration Not performed

122 Background: Most mCRC occurs in pts ≥50 y old but increasingly pts <50 y are being diagnosed with mCRC. Evidence regarding their outcomes is conflicting. BREAKWATER (Phase 3; NCT04607421) demonstrated statistically significant and clinically meaningful improvements in ORR, PFS by blinded independent central review (BICR), and OS with encorafenib + cetuximab (EC)+mFOLFOX6 vs control (chemotherapy±bevacizumab) in 1L BRAF V600E-mutant mCRC, making EC+mFOLFOX6 a new standard of care. We report analyses by age. Methods: Eligible pts with untreated BRAF V600E-mutant mCRC were randomized 1:1:1 to EC (n=158; enrollment closed after protocol amendment), EC+mFOLFOX6 (n=236), or control (n=243). Dual primary endpoints (EPs) were ORR and PFS by BICR; the key secondary EP was OS for EC+mFOLFOX6 vs control. Here, exploratory efficacy, safety, and biomarker analyses were performed by age at diagnosis (<50 y, early onset [EOCRC] or ≥50 y, average age onset [AOCRC]). A genAI tool (08/06/25; Pfizer; GPT-4o) assisted with the 1st draft; authors assume content responsibility. Results: As of Jan 6, 2025, 39, 66, and 59 EOCRC pts (~25% of each arm) were enrolled in the EC, EC+mFOLFOX6, and control arms, respectively, with 119, 170, and 184 AOCRC pts in each arm, respectively (Table). Median age (range) was 41 (24, 49) y for EOCRC pts and 64 (50, 84) y for AOCRC pts. Results for EC+mFOLFOX6 in EOCRC and AOCRC pts, respectively, were 69.7% and 64.1% for confirmed ORR by BICR, 10.9 and 14.0 mo for mPFS by BICR, and 23.8 and 30.3 mo for mOS. Results for the control arms in EOCRC and AOCRC pts, respectively, were 45.8% and 34.8% for confirmed ORR by BICR, 7.1 mo in both groups for mPFS by BICR, and 15.1 and 14.9 mo for mOS. See table for EC data. Incidence of grade 3/4 AEs was 80.0% and 82.0% for EC+mFOLFOX6, 64.8% and 67.4% for control, and 35.1% and 44.8% for EC in EOCRC and AOCRC pts, respectively. Biomarker data will be reported. Conclusions: All pts with BRAF V600E-mutant mCRC receiving 1L EC+mFOLFOX6, including EOCRC pts, showed improved ORR, PFS, and OS vs control. The safety profile of EC+mFOLFOX6 was similar for both age groups. Clinical trial information: NCT04607421 . EOCRC EOCRC EOCRC AOCRC AOCRC AOCRC EC n=39 EC+ mFOLFOX6 n=66 Control n=59 EC n=119 EC+ mFOLFOX6 n=170 Control n=184 Confirmed ORR, a % (95% CI) 56.4(41.0, 70.7) 69.7(57.8, 79.4) 45.8(33.7, 58.3) 42.0(33.5, 51.0) 64.1(56.7, 70.9) 34.8(28.3, 41.9) Odds ratio vs control (95% CI) 1.53(0.68, 3.46) 2.73(1.31, 5.68) 1.36(0.85, 2.18) 3.35(2.17, 5.18) Median PFS, a mo(95% CI) 5.4(4.2, 5.7) 10.9(9.7, 16.8) 7.1(6.7, 11.1) 8.3(6.4, 9.2) 14.0(11.3, 16.6) 7.1(5.9, 8.8) HR vs control(95% CI) 1.84(1.08, 3.13) 0.57(0.34, 0.95) 0.94(0.70, 1.27) 0.49(0.37, 0.65) Median OS, mo(95% CI) 18.9(14.6, 23.4) 23.8(21.1, NE) 15.1(13.2, 19.5) 19.5(17.6, 24.5) 30.3(21.0, NE) 14.9(13.7, 18.2) HR vs control(95% CI) 0.68(0.40, 1.16) 0.42(0.25, 0.71) 0.70(0.52, 0.95) 0.51(0.38, 0.68) NE, not estimable. a By BICR.

505 Background: Portal vein thrombosis (PVT), although considered rare in the general population, has a prevalence that varies significantly depending on the underlying disease severity and imaging modality. Common predisposing conditions include cirrhosis, various malignancies, and inflammatory and infectious processes. Our study aims to identify PVT events in patients with hepatocellular carcinoma (HCC), assess mortality and associated variables, and evaluate readmission causes. Methods: HCC adults(≥18 years) admitted with PVT as the primary diagnoses during the index admission were queried from the Nationwide Readmissions Database (NRD 2016-2022) using pretested ICD-10 codes. COVID positive cases were excluded from both index admissions and readmissions. The mortality rate during index admission was calculated and we used multivariable regression models to identify factors that could be linked with index mortality. We then estimated the 30-day readmission rates among survivors, and the mortality rate among readmissions and possible causes were also sought. Results: We found 1556 cases of PVT during index admission, of which 100(6.43%) died during the same admission. The majority of the index admissions were males (74.47%) with a mean age of 64.28 years. Of those who survived, 297(19.1%) were discharged as home health care. Higher odds of death during index admission were found in patients with cachexia (aOR 6.30, 95% CI 1.59-2.05), metastasis (aOR 7.45, 95% CI 2.92-18.98), acute/subacute liver failure (aOR 7.03, 95% CI 2.35-21.07), encephalopathy (aOR 5.62, 95% CI 1.83-17.23), acute kidney injury(AKI)(aOR 9.53, 95% CI 3.89-23.37), reported myocardial infarction during their stay (aOR 22.86, 95% CI 1.89-277.08) and those using palliative care (aOR 7.43, 95% CI 2.62-21.07), (p<0.05 throughout). Mean ages of patients who died versus those who survived the index admission were 65.42 versus 64.20 years (aOR 1.03, 95% CI 0.98-1.08, p=0.203). No significant differences in index mortality were found based on sex, insurance type, weekend admission, year of admission, or comorbidities including dyslipidemia, smoking, diabetes, chronic kidney disease, obesity, COPD, liver cirrhosis, frailty status, heart failure, presence of ascites, or reported ischemic stroke. Among those who survived, 32.55% were readmitted within 30 days, with 9.18% having a primary diagnosis of sepsis and 4.17% due to recurrent PVT. The mortality rate following readmission was 18.59%. Conclusions: In conclusion, certain underlying conditions increase the odds of inpatient death among HCC patients with PVT. The higher readmission mortality was primarily due to the occurrence of intercurrent illnesses, with sepsis being one of the leading factors. The higher mortality and readmission rates among cancer patients warrant improved management, education, and research initiatives.

TPS277 Background: Effective treatment for patients with metastatic colorectal cancer (mCRC) who have progressed on first-line therapy remains a significant unmet clinical need. BOLD-100 is a novel, first-in-class ruthenium-based anticancer therapeutic that has a unique, multimodal mechanism of action to kill cancer cells. Unlike traditional chemotherapy drugs that often target a single pathway, BOLD-100 works in several ways to overcome drug resistance and induce cell death, making it particularly effective when used in combination with other anticancer therapies. Data from the initial Phase 1/2 study of BOLD-100 plus FOLFOX (NCT04421820) indicated promising antitumor activity and well tolerated safety profile in patients with refractory mCRC (O'Kane, G. M., et al. Annals of Oncology 35 (2024): S22.). In addition, there was an unexpected reduction in oxaliplatin-induced peripheral neuropathy (OIPN) even in previously treated oxaliplatin patients. The efficacy and safety profile of this combination boosts its potential clinical benefit (Kumar, Ashish, et al. Abstract LB432: Cancer Research 85.8_Supplement_2 (2025)). Herein, we describe a phase 2 study comparing BOLD-100 plus FOLFOX with standard of care (FOLFOX) for the 2L treatment of patients with mCRC. Methods: BOLD-100-001 (NCT04421820) is a prospective, open-label, randomized global phase 2 study in patients with metastatic adenocarcinoma of the colon/rectum with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, ECOG performance status 0–1 and BRAF wildtype tumor status. Patients must have received only 1 prior line of treatment in the metastatic setting. Prior oxaliplatin is permitted if: 1) received in the adjuvant setting; 2) received in first line setting with no progression on treatment or within 3 months of oxaliplatin treatment cessation. Concurrent treatment with monoclonal antibody therapy (anti-EGFR, anti-VEGF, or anti-HER2) is not allowed. Patients will be randomized 1:1:1 to one of three cohorts: BOLD-100 at 500 mg/m² plus FOLFOX (Cohort 1), BOLD-100 at 625 mg/m² plus FOLFOX (Cohort 2), or FOLFOX alone (Cohort 3) and stratified by tumor sidedness (left vs right), KRAS mutation status (wild-type vs mutant), and geographical region (South Korea vs other). Primary objectives are to evaluate progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) by RECIST v1.1. Secondary safety objectives include evaluations of adverse event data, vital signs, and clinical laboratory testing. Exploratory objectives include assessment of duration of response (DOR), changes in biomarkers, and health-related quality of life and neuropathy-related quality of life per EORTC-QLQ-30 and EORTC-QLQ-CIPN20 scores. 120 patients are expected to be enrolled. Enrollment is ongoing at sites in Canada, South Korea and Europe. Clinical trial information: NCT04421820 .

90 Background: For Lynch syndrome (LS)-associated colorectal cancers(CRC), existing guidelines prefer extended resection for cancer risk reduction. However, life-long compromises in bowel function can result. As patients increasingly value shared decision-making, we evaluated the long-term outcome of a judicious conservative surgical approach allowing colorectal organ-preservation in LS. Methods: LS patients presenting with index (first-in-life) CRC between 2006-2023 were reviewed for clinical and surveillance data. LS was defined by pathogenic germline mutation. Shared decision-making was standard; extended resection was undertaken for patient choice, left-sided colon cancer, synchronous neoplasms. Primary outcome was organ preservation, defined as retaining the majority (>50%) of the colorectum, from index CRC to last contact. Results: Over 17 years, 273 patients presented with 302 index CRCs (233 [77.1%] colon, 69 [22.2%] rectal, with 29 [9.6%] being synchronous). Extended vs. segmental resections were performed in 26 (9.5%) vs. 201(73.6%) patients. The remaining 46 (16.9%) patients had no resection (advanced endoscopic resection in 9, complete clinical response in 21, and asymptotic primary with advanced metastases in 16). The immediate organ preservation rate was 90.5% (89.9% among 257 curative-intent cases). After 1741 person-years of follow-up (mean 6.4+5.5 years), 23 metachronous CRCs underwent repeat surgical (20) or endoscopic (3) resections. The long-term organ preservation rate was 83.2% (82.1% among curative-intent cases). The rate was higher among patients with index rectal cancers. Conclusions: Over 80% of LS patient enjoyed long-term colorectal organ preservation with a judicious conversative surgical approach. It should be strongly considered in the current era of endoscopic advances, immunotherapy, and novel prevention options.

443 Background: Neoadjuvant chemoradiation (nCRT) remains a standard of care in esophageal cancer. Although adjuvant Nivolumab improves progression-free survival (PFS), 5-year overall survival (OS) remains suboptimal. It is uncertain if PDL1 expression is a useful predictive biomarker in this setting. This study prospectively evaluated intratumoral immune changes after nCRT and their associations with clinical outcomes. Methods: All patients were treated with the CROSS regimen (41.4Gy in 23 fractions with weekly paclitaxel & carboplatin) followed by surgery. Multiplex immunofluorescence was performed on paired pre-CRT and post-CRT FFPE sections, staining for CK, CD3, CD8, CD68, FOXP3 and PDL1. Images were captured using Zeiss Axioscan 7 slide scanner and analyzed by a pathologist using HALO v3.6 software. The average percentage staining was calculated. Pathological tumor response was centrally reviewed. Data were presented as median (IQR). Changes in the immune cell densities before and after nCRT were compared using Wilcoxon signed-rank test. Locoregional recurrence-free survival (LRRFS), PFS and OS were defined from time of diagnosis. Univariate Cox regression analysis was used to assess the effects of immune cell densities on survival outcomes. A p <0.05 was considered statistically significant. Results: Twenty patients (85% males, 75% SCC) were included. R0 resection and pathological complete response (pCR) were achieved in 55% (11/20) and 15% (3/20) of patients, respectively. Significant reduction in PDL1+ tumor cells (∆ -0.2%, IQR -2.1 – 0.0, p = 0.044), FOXP3+ regulatory T-cells (T reg ) (∆ -0.4%, IQR -0.6 – -0.2, p <0.001) and PDL1+ macrophages (∆ -0.4%, IQR -0.9 – 0.0, p = 0.014) were observed after CRT. No significant changes were observed in CD8+ T-cells and PDL1- tumor and immune cell densities. Pre-CRT and post-CRT changes in immune cell densities did not differ between pCR and non-pCR patients. Median follow-up was 6.0 years (3.4 – 6.4) for all patients. On univariate Cox regression, only circumferential resection margin (CRM) was associated with PFS (HR 0.20, 95% CI 0.06 - 0.69, p = 0.011) and OS (HR 0.11, 95% CI 0.02 - 0.54, p = 0.007). Pre-CRT and changes in immune cell densities after nCRT, pCR status, histology and gender were not associated with DFS, LRRFS and OS. Interestingly, one patient received adjuvant Nivolumab when this became standard-of-care but relapsed within 1 year of surgery. This patient had a reduction in PDL1+ tumour cells (0.2%) and PDL1+ macrophages (0.2%) after nCRT. Conclusions: Neoadjuvant CRT led to significant reduction in immunosuppressive cells including PDL1+ tumour and immune cells, and T reg . However, these changes were not associated with pCR or survival in this small study. Larger confirmatory studies are needed to guide future biomarker-driven adjuvant strategies in esophageal cancer.

171 Background: Colorectal cancer (CRC) is the second most common cause of cancer-related mortality after lung cancer. Third-line treatments for metastatic CRC (mCRC) consists of regorafenib, fruquintinib, trifluridine-tipiracil plus bevacizumab. This study aims to compare the safety and efficacy of regorafenib versus fruquintinib in the treatment of mCRC. Methods: We retrieved data from phase II/III and phase III clinical trials published between (2012-2021). A meta-analysis was conducted for the patients’ demographics, overall survival (OS), progression-free survival (PFS), and the incidence of adverse events (AEs). We reconstructed individual patient data (IPD) from Kaplan-Meier (KM) curves to allow for indirect comparisons between studies. This study strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Our study included studies with 1389 patients. Of these, 650 patients received regorafenib and 739 received fruquintinib as third line for mCRC. Analysis revealed a median OS of 7.04 months (95% CI: 6.09-8.29) in the regorafenib arm versus a median OS of 7.96 months (95% CI: 7.40-8.77), with a hazard ratio (HR) of 0.87 (95% CI: 0.76-1.01; p= 0.07) in the fruquintinib arm. On the other hand, median PFS for both regorafenib and fruquintinib arms were 2.11 months (95% CI: 1.92-2.88) and 3.70 months (95% CI: 3.67-3.78), respectively. HR 0.71 (95% CI: 0.62-0.82, p<0.001). Conclusions: The results of our study revealed PFS analyses has shown superior outcomes in the fruquintinib arm compared to regorafenib. These findings suggest that fruquintinib may offer a more favorable disease control profile. Further studies are needed to confirm these findings and to better define the optimal selection of therapy in this patient population.

507 Background: Cholangiocarcinoma (CCA), categorized as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA), is often diagnosed at an advanced or metastatic stage. Approximately, 10-15% of iCCA harbor mutations in isocitrate dehydrogenase 1 ( IDH1 ) gene. However, data on real-world clinical outcomes and treatment patterns remain scarce. This study aims to provide a better understanding of the management of patients (pts) with m IDH1 CCA. Methods: This retrospective study utilized Citizen Health data, a real-world dataset harmonized across 3000 healthcare institutions, to evaluate United States CCA pts’ basic characteristics, molecular testing data, and treatment patterns. Pts were followed from the date of initial pathologic diagnosis until death or censored at the last activity in the database. In addition to the descriptive analysis, time-to-event endpoints were estimated using Kaplan-Meier (KM). Results: 602 pts diagnosed with CCA from 2007 to 2025 were included; 59.8% were female, median (range) age was 59.5 (22.3-85.8) years; 157 pts (26.1%) had ECOG performance Status 0 and 236 pts (39.2%) of 1. Most pts had iCCA (61.0%) and advanced or metastatic disease (59.8%) at diagnosis. The majority of pts (n=499, 82.9%) underwent biomarker testing. For 395 pts (79.2%), the testing was tissue-based and, for 106 pts (21.2%), it was performed on liquid biopsy. The main method used was next-generation sequencing (NGS) for 275 pts (55.1%) and immunohistochemistry (IHC) for 194 pts (38.9%). Among pts evaluated for IDH1 alterations, 88 pts (18.6%) had m IDH1 CCA with 60 pts (68.2%) diagnosed with advanced/metastatic disease. 80 pts (90.9%) received first-line (1L) systemic therapy for any stage, including gemcitabine-cisplatin (GemCis) (n=26, 32.5%) or GemCis-durvalumab (n=21, 26.3%) and GemCis-nab-paclitaxel (n=12, 15.0%). In the 1L, median (m) PFS was 8.0 months (mo), mOS was 30.0 mo, and disease control rate (DCR) was 84%. 63 pts (71.6%) received second-line (2L) therapy, including ivosidenib monotherapy (n=22; 34.9%) or in combination (n=7, 11.1%). In the 2L, in pts who received ivo-containing regimens (n=29), mPFS was 6.1 mo, mOS was 25.1 mo, and DCR was 69%; while in pts who received other regimens (n=34), mPFS was 4.1 mo, mOS was 20.1 mo, and DCR was 56%. Conclusions: Most pts with CCA were diagnosed with advanced or metastatic disease and the majority of pts had access to biomarker testing. Pts with m IDH1 CCA received mainly GemCis or GemCis-durvalumab as 1L therapy and ivosidenib as 2L therapy as recommended by current guidelines. mOS was longer than expected in each line of treatment, potentially due to survivorship bias, self-selection bias, and a limited number of pts harboring IDH1 mutations. This real-world study corroborates the efficacy finding from ClarIDHy and supports ivosidenib as a valuable 2L treatment option for patients with m IDH1 CCA.