FOCUS phase 3 trial results: Percutaneous hepatic perfusion (PHP) with melphalan for patients with ocular melanoma liver metastases (PHP-OCM-301/301A).
Authors: Zager Jonathan S. , Orloff Marlana M. , Ferrucci Pier Francesco , Glazer Evan Scott , Ejaz Aslam , Richtig Erika , Ochsenreither Sebastian , Lowe Michael C. , Reddy Sunil A. , Beasley Georgia , Gesierich Anja , Dummer Reinhard , Arance Ana Maria , Fenwick Stephen William , Wheater Matthew , Ottensmeier Christian 
Published: June 2022

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Background: Ocular melanoma, the most common intraocular malignancy, frequently metastasizes to the liver but to date there is no established standard of care for hepatic-dominant ocular melanoma patients. The FOCUS trial began as a randomized, Ph 3 trial (301) comparing PHP with best alternative care (BAC). The trial was subsequently amended (301A) to halt the BAC arm due to enrollment concerns. Methods: Eligible patients with hepatic-dominant ocular melanoma were randomized 1:1 to receive PHP or BAC (investigator’s choice of TACE, pembrolizumab, ipilimumab, or dacarbazine) on the 301 trial. All eligible patients received PHP on the 301A trial. PHP patients could receive up to 6 PHP treatments, repeated every 6-8 weeks with melphalan dosed at 3.0mg/kg ideal body weight (IBW). Patients with progressive disease (PD) were discontinued from study treatment and all patients are followed until death. Patientswere imaged every 12 (±2) weeks until PD. The primary endpoint, ORR (per RECIST 1.1) as assessed by Independent Review Committee, was characterized by the point estimate and 95% CI for each group (PHP and BAC). Results: 144 patients were enrolled overall; 102 were assigned to PHP (301: n = 43; 301A: n = 59) and 42 were assigned to BAC. 91 PHP patients received treatment (301: n = 40; 301A: n = 51) and 32 BAC patients received treatment. ORR among PHP patients was 35.2% (32/91; 95% CI: 25.44-45.88%). ORR among BAC patients was 12.5% (4/32; 95% CI: 3.51-28.99%; p= 0.0154). The median DOR was 14 months for PHP patients and not calculable for BAC patients. The DCR among PHP patients was 73.6% (67/91; 95% CI: 63.35-82.31%) and among BAC patients was 37.5% (12/32; 95% CI: 21.10-56.31%; p= 0.0002). The median PFS was 9.03 months (95% CI: 6.34-11.56) among PHP patients and was 3.12 months (95% CI: 2.89-5.65) among BAC patients ( p= 0.0007). The median OS was 20.53 months (95% CI: 16.59-24.35) among PHP patients and was 14.06 months (95% CI: 9.99-19.78) among BAC patients. With the last treatment occurring in May 2021, the OS, DOR, and PFS data continues to mature as patients are still being followed for survival. Among the 94 patients assessed for safety after treatment with PHP, 42.6% of patients experienced a serious treatment-emergent adverse event, the majority of which were hematological, transient in nature, and resolved without sequelae. There were no treatment related deaths in the trial. Conclusions: In this analysis of data from the FOCUS trial, PHP demonstrates superior ORR, DOR, DCR, PFS, and OS in comparison with BAC in the treatment of hepatic metastases from ocular melanoma. This therapy offers a potential option for patients with this rare indication that is associated with a poor prognosis and few treatment options. Clinical trial information: NCT02678572.