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

Content Provider	Europe PMC
Author	Rossi, Ernesto Cellini, Francesco Pagliara, Monica Maria Sammarco, Maria Grazia Pedone, Romina Rose Lancellotta, Valentina Tagliaferri, Luca Quirino, Michela Gambacorta, Maria Antonietta Blasi, Maria Antonietta Tortora, Giampaolo Schinzari, Giovanni
Editor	Roselli, Mario Ferroni, Patrizia Guadagni, Fiorella
Copyright Year	2023
Abstract	Simple SummaryUveal 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.AbstractUveal 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.
Journal	Cancers
Volume Number	15
PubMed Central reference number	PMC9857311
Issue Number	2
PubMed reference number	36672442
e-ISSN	20726694
DOI	10.3390/cancers15020493
Language	English
Publisher	MDPI
Publisher Date	2023-01-13
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors.
Subject Keyword	uveal melanoma liver metastases immunotherapy hepatic radiotherapy anti-PD-1 immune checkpoint liver directed therapies pembrolizumab tebentafusp
Content Type	Text
Resource Type	Article
Subject	Oncology Cancer Research