Adjuvant Sunitinib in High-Risk Patients with Uveal Melanoma: Comparison with Institutional Controls

Ophthalmology. 2018 Feb;125(2):210-217. doi: 10.1016/j.ophtha.2017.08.017. Epub 2017 Sep 19.

Abstract

Purpose: To compare overall survival in high-risk patients with primary uveal melanoma who received adjuvant sunitinib with institutional controls.

Design: Retrospective cohort.

Participants: Selection criteria were (1) monosomy 3 and 8q amplification by cytogenetic or DecisionDx-UM Class 2 and (2) monosomy 3 and large tumor size (T3-4 by American Joint Committee on Cancer classification). Exclusion criteria were date of diagnosis before 2007 or after 2013 and age <18 years.

Methods: A cohort of patients who intended to receive adjuvant sunitinib for 6 months was compared with institutional historical controls with the same risk factors. Kaplan-Meier and Cox proportional hazards models were used to analyze the outcome. Propensity score was used to adjust for nonrandom assignment to sunitinib.

Main outcome measures: Overall survival.

Results: From the Wills Eye Hospital Oncology Service Uveal Melanoma Cytogenetic Database (N = 1172), 128 patients fulfilled the selection and exclusion criteria. Median follow-up was 52.7 months (range, 0.26-108 months). A total of 54 patients received sunitinib. Their median age was 56 years (range, 29-81 years), and 48% were men. A total of 74 historical controls in the same risk category were identified. Their median age was 62 years (21-80 years), and 48% were men. Patients in the sunitinib group had worse cytogenetic or molecular features (monosomy 3 and 8q amplification or class 2 87% vs. 57%; P < 0.001), had smaller tumor sizes (T3-4 56% vs. 83%; P = 0.001), and were younger. There were 51 deaths, 14 (26%) in the sunitinib group and 37 (50%) in the control group. In the univariate analysis, the sunitinib group had longer overall survival (hazard ratio, 0.53; 95% confidence interval, 0.29-0.99; P = 0.041). In multivariate Cox regression analysis, interaction between use of sunitinib and age as a dichotomous variable was highly significant (P = 0.003). The following variables were statistically associated with prediction of overall survival: cytogenetic/molecular status (P = 0.015), T-size category (P = 0.022), gender (P = 0.040), and adjuvant sunitinib in patients aged <60 years (P = 0.004). Results were confirmed by propensity score analysis.

Conclusions: In this retrospective study, the use of sunitinib in the adjuvant setting was associated with better overall survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Chemotherapy, Adjuvant
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Indoles / administration & dosage*
  • Male
  • Melanoma / diagnosis
  • Melanoma / epidemiology
  • Melanoma / therapy*
  • Middle Aged
  • Proportional Hazards Models
  • Pyrroles / administration & dosage*
  • Retrospective Studies
  • Risk Assessment*
  • Sunitinib
  • Survival Rate / trends
  • Treatment Outcome
  • United States / epidemiology
  • Uveal Melanoma
  • Uveal Neoplasms / diagnosis
  • Uveal Neoplasms / epidemiology
  • Uveal Neoplasms / therapy*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Sunitinib