Work

Addressing screening failures in early-phase clinical trials in oncology: impact on patient outcomes and strategies for improvement

Year: 2025

Type: article

Abstract: BACKGROUND: Early-phase trials (EPT) assess efficacy/safety of new drugs that may represent therapeutic opportunities. Considering the stringent eligibility criteria, the screening process can result in high rate of screen failure (SF). We aimed to identify reasons for SF in patients who were initially deemed eligible and their prognostic factors. PATIENTS AND METHODS: Patients with solid tumors who consented to participate in EPT yet screen failed between 2020 and 2022 across three French cancer centers were retrospectively included. We collected demographic data, Eastern Cooperative Oncology Group (ECOG) performance status (PS), Royal Marsden Hospital (RMH) score upon signature, reason for SF and survival data. RESULTS: A total of 202 patients failed to enroll in EPT, representing an SF rate of 21.7% (Gustave Roussy Cancer Campus Villejuif), 21.4% (Oncopole Claudius Regaud, Toulouse) and 26.4% (Centre Léon Bérard, Lyon). Median age was 60 years (range 20-86 years); patients were mainly PS1 (n = 136, 67.3%). SF reasons were radiological (n = 59, 29.2%), biological (n = 48, 23.8%; n = 34 due to vital organ dysfunction), clinical (n = 45, 22.3%), administrative (n = 22, 10.9%), and PS deterioration (n = 24, 11.9%), and two patients died. Radiological reasons included brain metastases (n = 27), nonmeasurable disease (n = 17) and absence of target for mandatory biopsy (n = 8). Three-month mortality rate after SF was 30.2%, significantly related to biological (26.2%), clinical (26.2%) and PS deterioration (21.3%) (P = 0.012). Two-thirds of patients with newly discovered brain metastases were alive at 3 months (n = 18/27, 66.7%). Median follow-up was 24.6 months (19.6-26.9 months), 6-month overall survival was 47.5% (4.0-7.1 months). In the multivariable analysis adjusted for PS, location of metastatic sites and number of lines, RMH score remained significantly associated with OS (HR 2.20, P < 0.001). SF patients with RMH score of 0-1 presented an OS close to enrolled patients. CONCLUSIONS: Main reasons for SF were radiological, biological and clinical. Therefore, referring patients with brain scan and laboratory results may help reduce SF rates. Current criteria deem ineligible 47.5% of patients who are alive at 6 months, questioning their accuracy for patient selection in EPT whose aim is to evaluate drug tolerance/activity.

Source: ESMO Open

DOI: 10.1016/j.esmoop.2025.105331