TY - JOUR
T1 - 15-Gene Expression Profile and PRAME as Integrated Prognostic Test for Uveal Melanoma
T2 - First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1)
AU - Harbour, J. William
AU - Correa, Zelia M.
AU - Schefler, Amy C.
AU - Mruthyunjaya, Prithvi
AU - Materin, Miguel A.
AU - Aaberg, Thomas A.
AU - Skalet, Alison H.
AU - Reichstein, David A.
AU - Weis, Ezekiel
AU - Kim, Ivana K.
AU - Fuller, Timothy S.
AU - Demirci, Hakan
AU - Piggott, Kisha D.
AU - Williams, Basil K.
AU - Shildkrot, Eugene
AU - Capone, Antonio
AU - Oliver, Scott C.
AU - Walter, Scott D.
AU - Mason, John
AU - Char, Devron H.
AU - Altaweel, Michael
AU - Wells, Jill R.
AU - Duker, Jay S.
AU - Hovland, Peter G.
AU - Gombos, Dan S.
AU - Tsai, Tony
AU - Javid, Cameron
AU - Marr, Brian P.
AU - Gao, Ang
AU - Decatur, Christina L.
AU - Dollar, James J.
AU - Kurtenbach, Stefan
AU - Zhang, Song
N1 - Publisher Copyright:
© 2024 by American Society of Clinical Oncology.
PY - 2024/10/1
Y1 - 2024/10/1
N2 - PURPOSE 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 PRAME RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/PRAME classifier. MATERIALS This study included 1,577 patients with UM of the choroid and/or ciliary body AND METHODS 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 PRAME expression status (negative or positive) were available for all patients. The primary end point was metastasis-free survival (MFS). RESULTS 15-GEP was class 1 in 1,082 (68.6%) and class 2 in 495 (31.4%) patients. PRAME 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/PRAME(–), 80.6% (95% CI, 73.9 to 87.9) for class 1/PRAME(1), 58.3% (95% CI, 51.1 to 66.4) for class 2/ PRAME(–), and 44.8% (95% CI, 37.9 to 52.8) for class 2/PRAME(1). 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]; P < .001), followed by PRAME status (HR, 1.82 [95% CI, 1.42 to 2.33]; P < .001). The only clinical variable demonstrating additional prognostic value was tumor diameter. CONCLUSION 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/PRAME 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.
AB - PURPOSE 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 PRAME RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/PRAME classifier. MATERIALS This study included 1,577 patients with UM of the choroid and/or ciliary body AND METHODS 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 PRAME expression status (negative or positive) were available for all patients. The primary end point was metastasis-free survival (MFS). RESULTS 15-GEP was class 1 in 1,082 (68.6%) and class 2 in 495 (31.4%) patients. PRAME 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/PRAME(–), 80.6% (95% CI, 73.9 to 87.9) for class 1/PRAME(1), 58.3% (95% CI, 51.1 to 66.4) for class 2/ PRAME(–), and 44.8% (95% CI, 37.9 to 52.8) for class 2/PRAME(1). 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]; P < .001), followed by PRAME status (HR, 1.82 [95% CI, 1.42 to 2.33]; P < .001). The only clinical variable demonstrating additional prognostic value was tumor diameter. CONCLUSION 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/PRAME 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.
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U2 - 10.1200/JCO.24.00447
DO - 10.1200/JCO.24.00447
M3 - Article
C2 - 39052972
AN - SCOPUS:85201016175
SN - 0732-183X
VL - 42
SP - 3319
EP - 3329
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 28
ER -