DISCUSSION
obesity, death, uveal melanoma, toxicity, uveal melanoma liver metastases, hepatic-dominant disease
OBESITY, INFILTRATION, OBESE, LIVER METASTASES, UVEAL MELANOMA, ADVERSE EVENTS, METASTATIC UVEAL MELANOMA, METASTASES, COMPLICATIONS
In this, to our knowledge, first analysis of a randomized controlled phase III trial of previously untreated patients with isolated uveal melanoma liver metastases, a single treatment with IHP with melphalan was well tolerated with a manageable toxicity profile and resulted in significantly higher response rates and improved hPFS and PFS than the investigator's choice of available treatments.The outcomes in control group patients were similar to those reported in other recent studies, confirming that the control group is representative, and there was no cross-over allowing for IHP in the control arm. The ORR was 4.5%, and the median PFS was 3.3 months in the control arm, similar to previously reported results on patients with metastatic uveal melanoma treated with chemotherapy or ICIs with a CTLA-4 or a PD-1 inhibitor.Previous knowledge of outcomes after IHP is primarily based on smaller, retrospective single-institution series, where Alexander et al reported the pioneering studies on IHP for uveal melanoma metastases with an ORR of 62% including 10% with CR.A recent phase III study, the FOCUS trial, compared PHP with the investigator's choice of transarterial chemoembolization, ipilimumab, pembrolizumab, or dacarbazine in patients with metastatic uveal melanoma with hepatic-dominant disease.An interesting development is the combination of IHP or PHP with systemic immunotherapy. Data have shown a correlation between OS and a high infiltration of CD8The incidence of SAEs was higher in patients receiving IHP compared with patients in the control group. The adverse events in the IHP group were mainly expected complications because of major surgery. However, there was one treatment-related death in the IHP group. The patient was severely obese, a factor discussed thoroughly by the investigators as a potential contributing cause of death, and a new inclusion criterion of a BMI < 35 was added. The risks associated with obesity and IHP are probably related to obesity being a risk factor for surgery in general and not directly to IHP specifically. In comparison with PHP,In summary, the present randomized controlled trial shows that a one-time treatment with IHP results in significantly superior antitumor responses and PFS compared with treatment with chemotherapy or ICIs in treatment-naïve patients with isolated liver metastases of uveal melanoma. The first analysis of OS, the primary end point of the study, is planned for 2023.