Hepatic Radiotherapy in Addition to Anti-PD-1 for the Treatment of Metastatic Uveal Melanoma Patients

SIMPLE SUMMARY: Uveal melanoma often metastasizes to the liver. Immune checkpoint inhibitors showed low efficacy in this disease. Liver directed therapies are widely employed despite limited results. The addition of hepatic radiotherapy to anti-PD-1 could enhance the efficacy of immune checkpoint inhibitor alone. In this study, efficacy and safety of radiotherapy on liver metastases combined with pembrolizumab have been retrospectively analyzed in previously untreated metastatic patients. This combination allowed encouraging results without increasing toxicity of anti-PD-1. Therefore, hepatic radiotherapy and anti-PD-1 can be considered a valid choice for untreated HLA A 02:01 negative patients as well as for second line systemic therapy after tebentafusp. Prospective trials should be conducted to confirm these observations. ABSTRACT: Uveal melanoma is the most common ocular tumor with frequent metastatic spread to the liver. Immune checkpoint inhibitors have demonstrated poor results in this disease. The addition of hepatic radiotherapy to anti-PD-1 could enhance the sensitivity to immunotherapy. In this study, patients treated with pembrolizumab and who have undergone hepatic radiotherapy have been retrospectively evaluated. Twenty-two patients have been considered. Six patients (27.3%) achieved a partial response and 3 (13.6%) a stable disease. Disease control rate was 40.9%. Thirteen patients (59.1%) had progression as best response. The median PFS was 4.8 months and 6 months PFS rate 45.4%. The median OS was 21.2 months, while 1 year OS rate was 72.7%. Longer survival was observed in patients who achieved a partial response on irradiated metastases (HR 0.23, 95% CI 0.06–0.83) or progressed after 6 months (HR 0.12—95% CI 0.03–0.44). No radiotherapy-related or grade 3–4 adverse events were reported. This study demonstrates that the addition of hepatic radiotherapy to anti-PD-1 treatment can be a valid option for the treatment of metastatic uveal melanoma, particularly for HLA A 02:01 negative patients. Prospective studies should be conducted to confirm these data.