Saj, Fen

PURPOSE EGFR alterations occur in a subset of biliary tract cancers (BTCs) and are often linked to disease progression and poor prognosis, yet targeted approaches remain underexplored. ERRFI1 , encoding the epidermal growth factor receptor (EGFR) inhibitor MIG6, is mutated in various cancers, including BTC, representing a potential predictive biomarker. We investigated whether loss of ERRFI1 function may enhance sensitivity to EGFR-targeted tyrosine kinase inhibitors (TKIs), presenting a potential therapeutic opportunity. METHODS This is a retrospective multicenter study of patients with BTC harboring ERRFI1 alterations. Data were extracted from electronic health records following institutional approval. ERRFI1 alterations were classified based on the alteration type, variant allele frequencies were documented, and coalterations were analyzed. Treatment outcomes including response, time to progression (TTP), overall survival (OS), safety profiles, and tumor marker kinetics were noted. RESULTS Fourteen BTC patients with ERRFI1 mutations were identified in our database; the median age was 50 years, 64% were males; all cases were intrahepatic cholangiocarcinomas. Common coalterations included IDH1 (36%), TP53 (29%), and ARID1A (29%). All patients received gemcitabine-cisplatin as first-line treatment, and 79% received immune checkpoint inhibitors. Eight patients (57%) received EGFR TKIs. Best responses to EGFR therapy included three partial responses (2 responses lasting >20 months), four stable diseases, and one progressive disease. The median TTP was 7 months (95% CI, 6 to 21 months). Treatment was well-tolerated: toxicities included rash (n = 2), transaminitis (n = 1), and diarrhea (n = 1). The median OS was 20 months (95% CI: 8-36 months); 50% remained alive at last follow-up. CONCLUSION ERRFI1 mutations represent actionable biomarkers in BTC, with EGFR-targeted therapy demonstrating meaningful clinical benefit in this heavily pretreated population. These findings support integration of ERRFI1 testing into routine molecular profiling of BTC and other EGFR-driven malignancies.

Abstract Background Eligibility criteria for clinical trials are crucial for maintaining safety and study integrity. However, overly restrictive criteria can result in unrepresentative trial populations, leading to gaps in understanding real‐world treatment efficacy. Addressing potentially modifiable exclusions (PMEs) could enhance trial accessibility and participation without compromising safety. Methods The authors retrospectively analyzed screen‐failed patients with biliary tract cancer or pancreatic cancer between August 2019 and November 2024 at The University of Texas MD Anderson Cancer Center. Screen‐failed patients were those who provided informed consent but did not participate for any reason. Clinical data were obtained from screening logs and electronic health records. PMEs were identified and validated by two independent medical oncologists. Results Of 585 screen‐failed patients from 18 trials, 509 were analyzed (367 with pancreatic cancer and 142 with biliary tract cancer) after excluding 76 because of incomplete data. Leading causes of screen failure were declined participation (19%), comorbidities (12%), suboptimal organ function (11%), absence of a biomarker (10%), and insufficient biospecimens (7%). Reasons for declining included preference for standard care (23%), travel (22%), and competing trials (5%). The authors identified 69 patients (13.6%) who had PMEs (primarily borderline laboratory abnormalities), including liver function (23%), kidney function (20%), platelet count (12%), hemoglobin (7%), and white blood cell count (6%) abnormalities. Other PMEs included previous or concurrent malignancies (9%) and viral hepatitis (4%). PMEs were evenly distributed across trials. Conclusions Rigid eligibility criteria exclude stable patients who might benefit from investigational treatments. Easing criteria related to incidental or asymptomatic laboratory abnormalities could broaden trial accessibility and improve enrollment in populations that are more representative of real‐world use.

e23011 Background: Eligibility criteria for clinical trials are crucial for maintaining safety and study integrity. However, they often exclude patients due to medical conditions that are not relevant, leading to gaps in understanding the real-world effectiveness of treatments. Addressing potentially modifiable exclusions (PMEs) could enhance accessibility and participation in trials without compromising safety, particularly given the low rates of enrollment. Methods: We retrospectively analyzed ‘screen-failed’ patients (those who were excluded after providing consent because they did not meet the eligibility criteria or other protocol requirements) with biliary tract (BTC) or pancreatic cancer (PDAC) between August 2019 and November 2024. Screening logs and electronic health records provided clinical data. PMEs were identified and validated by two independent medical oncologists. Results: Of 585 screen-failed patients from 18 trials, 76 were excluded due to incomplete data. Among the 509 patients analyzed (367-PDAC, 142-BTC), the leading causes of screen failure were declined participation (99, 19%), comorbidities (59, 12%), suboptimal organ function (56, 11%), absence of biomarker (49, 10%), and insufficient biospecimens (36, 7%). Among patients declining participation, reasons included preference for standard care (23%), travel (22%), competing trials (5%), adverse event concerns (4%), financial issues (3%), and unknown reasons (43%). Of the 509 patients deemed ineligible for study entry at screening, we identified 69 patients (13.6%) with PMEs, primarily related to borderline laboratory abnormalities: liver function (16, 23%), kidney function (14, 20%), platelet count (8, 12%), hemoglobin (5, 7%), and white blood cell count (4, 6%). Other PMEs included previous or concurrent malignancies (6, 9%) and viral hepatitis (3, 4%). PMEs were evenly distributed across trials. Notably, all screen-failed patients proceeded to receive standard therapy. Conclusions: This analysis underscores the potential for rigid eligibility criteria to exclude stable patients who might benefit from investigational treatments. Easing specific criteria, particularly those related to laboratory abnormalities, could broaden trial accessibility. Furthermore, examining the reasons for declined participation and addressing PMEs could help develop strategies to enhance trial enrollment.