15-Gene Expression Profile and PRAME as Integrated Prognostic Test for Uveal Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1)

• Published in: Journal of clinical oncology Vol. 42; no. 28; pp. JCO2400447 - 3329
• Main Authors: Harbour, J William, Correa, Zelia M, Schefler, Amy C, Mruthyunjaya, Prithvi, Materin, Miguel A, Aaberg, Jr, Thomas A, Skalet, Alison H, Reichstein, David A, Weis, Ezekiel, Kim, Ivana K, Fuller, Timothy S, Demirci, Hakan, Piggott, Kisha D, Williams, Basil K, Shildkrot, Eugene, Capone, Jr, Antonio, Oliver, Scott C, Walter, Scott D, Mason, 3rd, John, Char, Devron H, Altaweel, Michael, Wells, Jill R, Duker, Jay S, Hovland, Peter G, Gombos, Dan S, Tsai, Tony, Javid, Cameron, Marr, Brian P, Gao, Ang, Decatur, Christina L, Dollar, James J, Kurtenbach, Stefan, Zhang, Song
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health 01.10.2024
• Subjects: ORIGINAL REPORTS
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.24.00447

Validated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/ classifier. This study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers. Test results for 15-GEP (class 1 or class 2) and expression status (negative or positive) were available for all patients. The primary end point was metastasis-free survival (MFS). 15-GEP was class 1 in 1,082 (68.6%) and class 2 in 495 (31.4%) patients. status was negative in 1,106 (70.1%) and positive in 471 (29.9%) patients. Five-year MFS was 95.6% (95% CI, 93.9 to 97.4) for class 1/ (-), 80.6% (95% CI, 73.9 to 87.9) for class 1/ (+), 58.3% (95% CI, 51.1 to 66.4) for class 2/ (-), and 44.8% (95% CI, 37.9 to 52.8) for class 2/ (+). By multivariable Cox proportional hazards analysis, 15-GEP was the most important independent predictor of MFS (hazard ratio [HR], 5.95 [95% CI, 4.43 to 7.99]; .001), followed by status (HR, 1.82 [95% CI, 1.42 to 2.33]; .001). The only clinical variable demonstrating additional prognostic value was tumor diameter. In the largest prospective multicenter prognostic biomarker study performed to date in UM to our knowledge, the COOG2 study validated the superior prognostic accuracy of the integrated 15-GEP/ classifier over 15-GEP alone and clinical prognostic variables. Tumor diameter was found to be the only clinical variable to provide additional prognostic information. This prognostic classifier provides an advanced resource for risk-adjusted metastatic surveillance and adjuvant trial stratification in patients with UM.