Response to Anti-PD-1 in Uveal Melanoma Without High-Volume Liver Metastasis

J Natl Compr Canc Netw. 2019 Feb;17(2):114-117. doi: 10.6004/jnccn.2018.7070.

Abstract

Background: Uveal melanoma (UM) is an uncommon melanoma subtype with poor prognosis. Agents that have transformed the management of cutaneous melanoma have made minimal inroads in UM. Methods: We conducted a single-arm phase II study of pembrolizumab in patients with metastatic UM and performed bioinformatics analyses of publicly available datasets to characterize the activity of anti-PD-1 in this setting and to understand the mutational and immunologic profile of this disease. Results: A total of 5 patients received pembrolizumab in this study. Median overall survival was not reached, and median progression-free survival was 11.0 months. One patient experienced a complete response after one dose and 2 others experienced prolonged stable disease (20% response rate, 60% clinical benefit rate); 2 additional patients had rapidly progressing disease. Notably, the patients who benefited had either no liver metastases or small-volume disease, whereas patients with rapidly progressing disease had bulky liver involvement. We performed a bioinformatics analysis of The Cancer Genome Atlas for UM and confirmed a low mutation burden and low rates of T-cell inflammation. Note that the lack of T-cell inflammation strongly correlated with MYC pathway overexpression. Conclusions: Anti-PD-1-based therapy may cause clinical benefit in metastatic UM, seemingly more often in patients without bulky liver metastases. Lack of mutation burden and T-cell infiltration and MYC overexpression may be factors limiting therapeutic responses.ClinicalTrials.gov identifier: NCT02359851.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Computational Biology / methods
  • Gene Expression Profiling
  • Humans
  • Liver Neoplasms / secondary
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / mortality
  • Melanoma / pathology*
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism
  • Treatment Outcome
  • Uveal Neoplasms / drug therapy*
  • Uveal Neoplasms / genetics
  • Uveal Neoplasms / mortality
  • Uveal Neoplasms / pathology*

Substances

  • Antineoplastic Agents, Immunological
  • Programmed Cell Death 1 Receptor

Supplementary concepts

  • Uveal melanoma

Associated data

  • ClinicalTrials.gov/NCT02359851
  • ClinicalTrials.gov/NCT02359851