Determinants of overall survival in patients with metastatic uveal melanoma Journal Article


Authors: Demkowicz, P.; Pointdujour-Lim, R.; Miguez, S.; Lee, Y.; Jones, B. S. C. L.; Barker, C. A.; Bosenberg, M.; Abramson, D. H.; Shoushtari, A. N.; Kluger, H.; Francis, J. H.; Sznol, M.; Bakhoum, M. F.
Article Title: Determinants of overall survival in patients with metastatic uveal melanoma
Abstract: Background: Despite improvements in the treatment of primary uveal melanoma (UM), patients with metastatic disease continue to exhibit poor survival. Methods: A retrospective review of metastatic UM patients at Yale (initial cohort) and Memorial Sloan Kettering (validation cohort) was conducted. Cox proportional hazards regression was used to determine baseline factors that are associated with overall survival, including sex, Eastern Cooperative Oncology Group (ECOG) Performance Status Scale, laboratory measurements, metastasis location, and use of anti-CTLA-4 and anti-PD-1 therapies. Differences in overall survival were analyzed using Kaplan–Meier analysis. Results: A total of 89 patients with metastatic UM were identified; 71 and 18, in the initial and validation cohorts, respectively. In the initial cohort, median follow-up was 19.8 months (range, 2–127 months) and median overall survival was 21.8 months (95% CI, 16.6–31.3). Female sex, anti–CTLA-4, and anti–PD-1 therapy were associated with better survival outcomes with adjusted death hazard ratios (HRs) of 0.40 (95% CI, 0.20–0.78), 0.44 (0.20–0.97), and 0.42 (0.22–0.84), respectively, whereas development of hepatic metastases and ECOG score ≥1 (per 1 U/L) were associated with worse survival outcomes with HRs of 2.86 (1.28–7.13) and 2.84 (1.29–6.09), respectively. In both the initial and validation cohorts, use of immune checkpoint inhibitors was associated with improved overall survival after adjusting for sex and ECOG score, with death HRs of 0.22 (0.08–0.56) and 0.04 (0.002–0.26), respectively. Conclusions: Development of extrahepatic-only metastases, ECOG of 0, immune checkpoint therapy, and female sex were each associated with more than 2-fold reductions in risk of death. Plain Language Summary: Metastatic uveal melanoma patients face limited treatment options and poor survival rates. Results from this retrospective analysis indicate that immune checkpoint inhibitors, such as anti–CTLA-4 and anti–PD-1 therapies, were associated with improved survival outcomes. Factors such as extrahepatic-only metastases, better baseline performance status, and female sex contributed to a more than 2-fold reduction in death risk. These findings highlight the potential of immunotherapy in treating metastatic uveal melanoma. © 2023 American Cancer Society.
Keywords: retrospective studies; ipilimumab; melanoma; retrospective study; immunotherapy; uvea melanoma; uvea tumor; uveal neoplasms; uveal melanoma; retrospective cohort study; immune checkpoint inhibitor; nivolumab; humans; human; female; metastatic uveal melanoma; immune checkpoint inhibitors; tebentafusp
Journal Title: Cancer
Volume: 129
Issue: 20
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2023-10-15
Start Page: 3275
End Page: 3286
Language: English
DOI: 10.1002/cncr.34927
PUBMED: 37382208
PROVIDER: scopus
PMCID: PMC11149607
DOI/URL:
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- Source: Scopus
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MSK Authors
  1. Jasmine Helen Francis
    256 Francis
  2. David H Abramson
    389 Abramson
  3. Christopher Barker
    218 Barker