Dr DePalo on First-Line Therapies in Unresectable Melanoma In-Transit Metastases

Danielle K. DePalo, MD, Moffitt Cancer Center, discusses findings from a study comparing first-line isolated limb infusion/perfusion vs immune checkpoint inhibitors and intratumoral therapy in patients with surgically unresectable melanoma in-transit metastases.

Of the 560 patients included in the study, 86 had received intratumoral therapy, 353 had received isolated limb infusions/perfusions, and 121 had received immune checkpoint inhibitors. The patients in the intratumoral therapy cohort had the highest median age, at 74 years vs a median age of 67 years in the infusion/perfusion cohort and the lowest median age of 64 years in the immune checkpoint inhibitor cohort. Infusions/perfusions were used to treat the highest mean number of lesions, at a median of 12.6 vs 4.2 and 7.1 in the intratumoral therapy and immune checkpoint inhibitor cohorts, respectively. The largest median sizes of the in-transit metastases were comparable across the intratumoral therapy, infusion/perfusion, and immune checkpoint inhibitor cohorts, at 7 mm, 10 mm, and 12 mm, respectively, DePalo says.

The toxicity profiles followed expected patterns for each treatment modality, DePalo notes. Those in the infusion/perfusion cohort experienced higher rates of lymphedema, at 31.9% vs 12.2% and 19.5% in the intratumoral therapy and immune checkpoint inhibitor cohorts, respectively. The immune checkpoint inhibitor cohort had higher rates of toxicities requiring short-term pharmacological therapy, at 44.1% vs 18.0% and 20.4% in the intratumoral therapy and infusion/perfusion cohorts, respectively. This cohort also experienced higher rates of toxicities requiring hospitalization, at 22.1% vs 1.4% and 9.2% in the intratumoral therapy and infusion/perfusion cohorts, respectively.

The median follow-up was longest for the patients who received infusions/perfusions because limb infusions/perfusions have been used for a longer time than intratumoral therapies and immune checkpoint inhibitors, DePalo explains. Patients who received intratumoral therapy or infusions/perfusions had the highest overall response rates, at 72.1% and 82.2%, respectively, compared with 63.6% in those who received immune checkpoint inhibitors.

Patients who received intratumoral therapy achieved the longest median local progression-free survival (PFS), which was not reached (NR) vs 1.0 years and 1.6 years in those who received infusions/perfusions and immune checkpoint inhibitors, respectively. The median distant PFS was NR, 7.4 years, and 5.6 years in the intratumoral therapy, infusion/perfusion, and immune checkpoint inhibitor cohorts, respectively. These findings were supported by a multivariable analysis, and these patterns were also observed regarding melanoma-specific survival and overall survival, DePalo concludes.