The FOCUS study was the largest LDT (liver directed therapy) clinical trial undertaken in metastatic uveal melanoma.1-3
95 Patients were enrolled into the HEPZATO KIT arm; 91 patients received treatment.4,a
Patients could have limited extrahepatic disease in the bone, subcutaneous sites, lymph nodes, or lung if the life-threatening component of the UM was in the liver. Any extrahepatic disease needed to be amenable to resection or radiation, with a defined treatment plan.4
Treatment schedule
Patients received a dose of 3 mg/kg of melphalan using CHEMOSAT delivery system every 6 to 8 weeks for up to 6 treatment cycles.4,a
a Based on ideal body weight (IBW; maximum total dose, 220 mg)
More Than 1/3 of Patients Responded to Treatment With CHEMOSAT4
ORR reported in FOCUS was 36.3% (n = 33)4
Median DoR in responders (n = 33) was 14 months4,c
CR: Disappearance of all target lesionsa
PR: ≥30% Decrease in the sum of the long axis diameter of tumor target lesionsb
aAny pathological lymph nodes (target or nontarget) must be <10 mm in short-axis diameter. For nontarget lesions, disappearance of all nontarget lesions and normalization of tumor marker level.5
bUsing the baseline sum as reference.5
cCalculated using Kaplan-Meier method.4
Safety: Demonstrated
Safety & Tolerability4
ORR reported in FOCUS was 36.3% (n = 33)4
• Nausea • Fatigue • Musculoskeletal pain
• Abdominal pain • Vomiting
All adverse events observed at a frequency of >10% in patients
| All grades, % | Grades 3 or 4, % | |
|---|---|---|
| Gastrointestinal disorders | ||
| Nausea | 57 | 0 |
| Abdominal paina | 39 | 1 |
| Vomitinga | 35 | 0 |
| Diarrheaa | 17 | 1 |
| General disorders | ||
| Fatiguea | 65 | 0 |
| Pyrexiaa | 16 | 0 |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal paina | 46 | 1 |
| Groin pain | 11 | 0 |
| Respiratory disorders | ||
| Dyspneaa | 23 | 2 |
| Cougha | 15 | 0 |
| Nervous system disorders | ||
| Headachea | 19 | 0 |
| Lethargy | 12 | 0 |
| Dizzinessa | 11 | 0 |
| Injury and procedural complications | ||
| Contusion | 17 | 0 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 16 | 0 |
| Vascular disorders | ||
| Hemorrhagea | 15 | 1 |
| Hypotensiona | 13 | 3 |
aRepresents a composite of multiple, related preferred terms.
Serious adverse events occurred in 45% of patients who received treatment4
Serious adverse events occurring in ≥2% of patients were thrombocytopenia (10%), neutropenia (8%), febrile neutropenia (7%), platelet count decreased (6%), leukopenia (4.2%), cardiac arrest (3.2%), neutrophil count decreased (2.1%), hypoxia (2.1%), pleural effusion (2.1%), pulmonary edema (2.1%), and deep vein thrombosis (2.1%).4
Fatal adverse events occurred in 3 patients (3.2%) ; these included cardiac arrest, acute hepatic failure, and bacterial peritonitis and were deemed not to be related to treatment.4,6
Treatment was permanently discontinued because of adverse events in 18% of patients, with neutropenia being the most common reason (3.2%).4
Prospective & Retrospective Studies
Treatment naïve as well as previously treated patients have shown efficacy across various endpoints.
| N | Treatment Line | Patient Tumor Characteristics | ORR | OS | PFS | Safety | Reference | |
|---|---|---|---|---|---|---|---|---|
| Prospective Study | 35 | 60% treatment naïve |
No. of metastases ≥10 (57%) | 72% |
1 year OS - 77% 2 year OS - 43% mOS 19.1 months |
7.5 mPFS |
Majority developed grade 3/4 haematologic events 14 grade 3 non-haematologic events |
Meijer, T., et al 20207 |
| Retrospective Studies | 81 | 54% treatment naïve |
>10 lesions/>50% volume replacement (51.9%) | 60.5% | mOS 14.9 months | 8.4 mPFS |
Grade 3/4 events were observed in 27.7% of patients | Modi, S., et al 20228 |
| 51 | 43.1% treatment naïve |
Oligometastatic disease ≤ 3 deposits (23.5%)
>10 lesions/>50% volume replacement (31.4%) |
47% | mOS 15.3 months | 8.1 months |
37.5% grade 3-4 non-haematologic events | Karydis, I., et al 20171 | |
| 19 | 31% treatment naïve |
Not reported | 53% | mOS 16.7 months | 14.03 months |
2 cases grade 3a (coronary ischaemia)
1 case grade 3b (transfemoral bleeding with following surgery) |
Bruning, R., et al 20202 | |
| 16 | 25% treatment naïve |
Hepatic lesions ranged from 3 to >20
Median tumour load of 22.5% (interquartile range 10 to 25%) |
60% | mOS 27.4 months | 11.1 mPFS |
Grade 3/4 events were observed in 43.8% of patients | Artzner, C., et al 20199 |
ORR – overall response rate; PFS – progression free survival; mPFS – median progression free survival, OS – overall survival; mOS – median overall survival.
