Abstract A124: Prevalence, Treatment Patterns, and Outcomes of Organ Dysfunction at Diagnosis in Metastatic Pancreatic Ductal Adenocarcinoma: A Single-Institution Analysis of 3,022 Patients
Emma Cismas, Rebecca B. Forman, Jiayin Zheng, Qian Shi, Wungki Park, Michael Pishvaian, Jeffrey A. Meyerhardt, Eileen M. O'Reilly, Efrat Dotan, Michael MayAbstract
Background:
Patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) sometimes present with renal or hepatic dysfunction not due to readily reversible biliary obstruction. This dysfunction impacts clinical trial and treatment eligibility, but its prevalence and association with survival remain poorly characterized. We evaluated treatment patterns and outcomes of patients with mPDAC and organ dysfunction at diagnosis.
Methods:
We analyzed 3,022 patients who were diagnosed with mPDAC and underwent laboratory testing at Memorial Sloan Kettering 2014-2026. Patients with <30 days of follow-up (N=134) were excluded from treatment analyses. Four organ dysfunction categories were defined: renal dysfunction (eGFR <60 mL/min/1.73m2), hepatic transaminase elevation (AST or ALT >2.5x ULN), hypoalbuminemia (albumin <3 g/dL), and persistent hyperbilirubinemia (total bilirubin >1.8 mg/dL through day 30). Kaplan-Meier estimates and log-rank testing were used for mOS comparisons. A multivariable Cox model assessed the impact of these categories and age on mOS.
Results:
N=1030 (34%) patients had organ dysfunction at diagnosis, including 378 (13%) with renal dysfunction (135 [5%] with eGFR <45 mL/min/1.73m2), 508 (17%) with transaminase elevation, 160 (5%) with hypoalbuminemia, and 397 (13%) with persistent hyperbilirubinemia. The renal dysfunction group had the highest median age (75 vs 68 [25-95] in the full cohort, p<0.001) and a higher proportion of Black or African American patients (11.4% vs 7.2%, p=0.002). Treatment paradigms differed markedly between categories. Among patients with normal organ function, 82% received PDAC-directed treatment, most commonly FOLFIRINOX/NALIRIFOX (38%), gemcitabine with nab-paclitaxel (GNP, 16%) or experimental therapies (10%). Across organ dysfunction cohorts, 68% received treatment and only 3% received experimental therapies. Among patients with renal dysfunction, there was increased use of GNP (19% of patients) and gemcitabine monotherapy (12%) while FOLFOX was the most common treatment for patients with hyperbilirubinemia (30%). On multivariable Cox regression, all groups were independently associated with shorter mOS. mOS was 4.7 months for renal dysfunction (HR 1.22, p=0.001; 2.7 months for eGFR <45 mL/min/1.73m2), 5.3 months for transaminase elevation (HR 1.14, p=0.03), 1.3 months for hypoalbuminemia (HR 2.75, p<0.001), 4.3 months for persistent hyperbilirubinemia (HR 1.23, p=0.002) and 9.0 months for patients without organ dysfunction.
Conclusions:
We found that 34% of patients with mPDAC presented with organ dysfunction. These patients had worse mOS, unique treatment paradigms and were excluded from clinical trials. Novel therapies, such as daraxonrasib, are reshaping treatment paradigms in PDAC, but trials of these agents require normal organ function. Prospective investigation into the impact of organ dysfunction on the safety, tolerability, optimal dosing and efficacy of novel therapies will be critical in translating positive clinical trials into improvements for all patients with mPDAC.
Citation Format:
Emma Cismas, Rebecca B. Forman, Jiayin Zheng, Qian Shi, Wungki Park, Michael Pishvaian, Jeffrey A. Meyerhardt, Eileen M. O'Reilly, Efrat Dotan, Michael May. Prevalence, Treatment Patterns, and Outcomes of Organ Dysfunction at Diagnosis in Metastatic Pancreatic Ductal Adenocarcinoma: A Single-Institution Analysis of 3,022 Patients [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr A124.