Subgroup analyses of the phase 3 FOCUS study of melphalan/hepatic delivery system in patients with unresectable metastatic uveal melanoma.

PURPOSE: To assess efficacy and safety in subgroups of patients treated with Melphalan/Hepatic Delivery System (melphalan/HDS), a drug/device combination for liver-directed treatment of metastatic UM (mUM) patients. Previously reported FOCUS study results indicated melphalan/HDS treatment provides a clinically meaningful response rate and favorable benefit-risk ratio in patients with unresectable mUM.

METHODS

Patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) every 6-8 weeks for up to 6 cycles. Post hoc analyses of efficacy and safety were conducted for patient subgroups based on demographic and baseline disease characteristics.

RESULTS

102 patients with mUM were enrolled; treatment was attempted in 95 patients; 91 patients received treatment. Subgroup analyses showed consistent tumor response regardless of age, sex, geographic region, presence/absence of extrahepatic lesions, and prior therapy. Patients with lower tumor burden had better objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) than those with higher tumor burden (ORR: 51.1 vs. 22.2%, p = 0.008; mPFS: 11.3 vs. 5.8 months, p = 0.007; mOS: 26.7 vs. 15.4 months, p = 0.008). Patients with 1-25% liver involvement had higher mOS than those with 26-50% liver involvement (22.4 vs. 16.9 months; p = 0.030); patients with low or normal lactate dehydrogenase (LDH) had higher mOS than those with elevated LDH (23.5 vs. 15.3 months; p = 0.019). The overall safety profile was similar across subgroups without evidence of cumulative toxicity with successive treatment cycles.

CONCLUSION

Results demonstrate a favorable benefit-risk profile for melphalan/HDS across clinically relevant subgroups. However, early treatment in patients with low tumor burden may offer best results.