PROACTIF: Final results from the largest prospective real-world study of 1196 primary liver cancer patients (PLC) treated with yttrium-90 (Y90) glass transarterial radioembolization (TARE).

504 Background: This study evaluated the effectiveness, quality-of-life, safety, and dosimetry of Y90 glass microspheres for the treatment of primary and colorectal liver metastasis in a real-world clinical setting. Herein, we present the final data for patients with hepatocellular carcinoma HCC and intrahepatic cholangiocarcinoma iCCA. Methods: All patients treated with Y90 glass microspheres (TheraSphere) between 2019 and 2024 who agreed to data collection were included from 34 French institutions. Duration of follow-up and overall survival (OS) were assessed by reverse Kaplan-Meier (KM) and KM analysis, respectively. Toxicity was assessed using CTCAE v5. Pre/post-treatment dosimetry was re-assessed by central read using activity determined by the site. Results: In total, 1196 patients with PLC (989 HCC; 207 iCCA) were included. Of the HCC patients, 35.3% had portal vein thrombosis; 13.3%, 18.9%, 57.9%, and 5.8% were BCLC A, B, C, D, respectively. Among iCCA patients, 56.5% were ECOG 0; 31.9% had associated liver fibrosis or cirrhosis. At least one prior treatment was reported in 39% of PLC patients (systemic, n=194; locoregional LRT, n=289; surgery, n=72). Personalized multicompartment dosimetry was used for 73% of patients and selective treatment administration was used for 55%. By central assessment, pretreatment mean absorbed dose to total perfused tumor was 422.1 Gy in HCC and 357.2 Gy in iCCA. Median OS 95%CI was 21.8 months (M) 20.1 – 23.3 for HCC and 21.9M 18.2 – 24.3 for iCCA. iCCA patients treated with TARE as a first-line treatment had longer OS (23.3M) compared to patients treated as a second-line treatment (11.4M). More than half of PLC patients had subsequent treatment (54%). PLC patients who had post-Y90 surgery (12%) had the greatest OS benefit. In HCC, median OS was 48.6M with subsequent surgery (n=112), 23.3M with subsequent LRT or systemic treatment (n=424), and 14.8M with no further treatment (n=396). In iCCA, median OS was not reached in patients with subsequent surgery (n=27), 21.3M for patients with subsequent LRT or systemic treatment (n=90), and 17.4M for patients without subsequent treatment (n=76). Among all patients, 93 experienced adverse events (AEs; n=134), 88 had serious AEs (n=114), and 45 patients had related/possibly related serious treatment-emergent AEs (3.8%). Conclusions: Results from this large prospective real-world study using contemporary TARE treatment highlight its critical role as an integral component in the continuum of care for patients with PLC. In most cases, patients received personalized treatment, resulting in meaningful survival, and an acceptable adverse event profile. Importantly, TARE followed by surgery resulted in survival outcomes rarely observed in this population of patients typically not eligible for surgery. Clinical trial information: NCT04069468 .