High-dose 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) chemoembolization for treatment-naïve patients with limited uveal melanoma hepatic metastases.

9550 Background: Nearly 50% of patients with uveal melanoma (UM) develop metastases with the liver being the primary site of disease in > 90% of cases. Control of hepatic tumors is crucial to prolonging overall survival (OS) for metastatic uveal melanoma (MUM) patients. We report results of aPhase II prospective trial [NCT04728633] using high-dose BCNU chemoembolization (TACE) as first-line treatment for limited UM hepatic metastases. Methods: MUM patients with < 50% hepatic tumor burden and no significant extrahepatic disease were treated with hepatic artery infusion of 300mg of BCNU diluted in ethiodized oil followed by gelatin sponge embolization until maximum clinical benefit, hepatic and/or extrahepatic disease progression (PD), or development of significant adverse events (AE). Tumor response (RECIST 1.1) was assessed using CT and MRI. Treatment breaks were allowed for patients with disease control (partial response [PR] + stable disease [SD]) to reduce toxicities and optimize quality of life. Retreatment with TACE was permitted if PD occurred during treatment breaks. OS, progression-free survival from liver (PFS-L) and systemic metastases were analyzed. Toxicities were assessed using CTCAE v5.0. Results: Twenty-eight patients (17 men; median age, 62; range, 39 - 84) were enrolled from October 2021 to January 2025. Bilobar (n=25) or unilobar (n=3) BCNU TACE was performed every 4 or 7 weeks (+/- 7 days), respectively. Median follow-up was 11.6 months (range, 1.8 – 37.6). Median OS was 14.1 months (range, 1.8 – 37.6) with 13 surviving patients. Best treatment response included PR in 8, SD in 18, and PD in 2 patients for an overall response rate of 28.6% and a disease control rate of 92.9%. Twenty-two (78.6%) patients with disease control had treatment breaks. One patient withdrew from the trial to pursue percutaneous hepatic perfusion despite SD for 25 months. Median PFS-L was 9.9 months (range, 1.8 – 36.8). Sixteen (57.1%) patients developed new/nontarget hepatic tumor progression (n=13) or progression of target and nontarget lesions (n=3). Treatment-related grade 3 AEs included pain (n=5), hypertension (n=4), incidental pulmonary emboli (n=3), thrombocytopenia (n=1) and an infected biloma. Self-limiting grade 3 or 4 liver enzyme elevation occurred in 6 patients. Fifteen (53.6%) patients developed extrahepatic disease (median, 7.3 months); 11 patients (7 with stable liver tumors) started systemic therapy off-trial. Three patients developed life-limiting AEs due to checkpoint inhibitor therapy. Conclusions: High-dose BCNU TACE provided disease control in the majority of treatment-naïve patients with limited UM hepatic metastases. PD typically occurred during treatment breaks, as expected. Future trials exploring the combination of BCNU TACE with systemic therapies to address both hepatic and extrahepatic metastases are warranted. Clinical trial information: NCT04728633 .