Affiliation:
1. Yale University School of Medicine New Haven Connecticut USA
2. Department of Ophthalmology and Visual Science Yale University School of Medicine New Haven Connecticut USA
3. Institute of Dermatology & Oculoplastic Surgery Sarasota Florida USA
4. Department of Radiation Oncology Memorial Sloan Kettering Cancer Center New York New York USA
5. Department of Pathology Yale University School of Medicine New Haven Connecticut USA
6. Yale Cancer Center Yale University New Haven Connecticut USA
7. Department of Surgery Memorial Sloan Kettering Cancer Center New York New York USA
8. Department of Medicine Memorial Sloan Kettering Cancer Center New York New York USA
9. Department of Medicine Weill Cornell Medical College New York New York USA
10. Department of Medicine Yale University School of Medicine New Haven Connecticut USA
Abstract
AbstractBackgroundDespite improvements in the treatment of primary uveal melanoma (UM), patients with metastatic disease continue to exhibit poor survival.MethodsA 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.ResultsA 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.ConclusionsDevelopment 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 SummaryMetastatic 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.
Funder
National Cancer Institute