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)

Author:

Harbour J. William12ORCID,Correa Zelia M.34ORCID,Schefler Amy C.5,Mruthyunjaya Prithvi6ORCID,Materin Miguel A.7,Aaberg Thomas A.8,Skalet Alison H.910,Reichstein David A.11,Weis Ezekiel1213ORCID,Kim Ivana K.14ORCID,Fuller Timothy S.15ORCID,Demirci Hakan16,Piggott Kisha D.17,Williams Basil K.18ORCID,Shildkrot Eugene19ORCID,Capone Antonio20,Oliver Scott C.21ORCID,Walter Scott D.2223,Mason John24,Char Devron H.25,Altaweel Michael26ORCID,Wells Jill R.27,Duker Jay S.28,Hovland Peter G.29,Gombos Dan S.30,Tsai Tony31ORCID,Javid Cameron32,Marr Brian P.33,Gao Ang234,Decatur Christina L.34ORCID,Dollar James J.34ORCID,Kurtenbach Stefan34,Zhang Song234ORCID

Affiliation:

1. Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX

2. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX

3. Bascom Palmer Eye Institute and Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL

4. Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL

5. Retina Consultants of Texas, Houston, TX

6. Byers Eye Institute, Department of Ophthalmology, Stanford University, Stanford, CA

7. Department of Ophthalmology, Duke University, Durham, NC

8. Retina Specialists of Michigan, Foundation for Vision Research, and Michigan State University College of Human Medicine, Grand Rapids, MI

9. Casey Eye Institute, Oregon Health and Science University, Portland, OR

10. Knight Cancer Institute, Oregon Health and Science University, Portland, OR

11. Tennessee Retina, Nashville, TN

12. Department of Ophthalmology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada

13. Division of Ophthalmology, Department of Surgery, Faculty of Medicine, University of Calgary, Calgary, Canada

14. Massachusetts Eye and Ear Infirmary and Department of Ophthalmology, Harvard Medical School, Boston, MA

15. Texas Retina Associates, Dallas, TX

16. Kellogg Eye Center and Department of Ophthalmology, University of Michigan, Ann Arbor, MI

17. Department of Ophthalmology and Visual Sciences, Washington University, St Louis, MO

18. Department of Ophthalmology, University of Cincinnati, Cincinnati, OH

19. Department of Ophthalmology, University of Virginia, Charlottesville, VA

20. Associated Retina Consultants, Royal Oak, MI

21. Sue Anschutz-Rodgers Eye Center and Department of Ophthalmology, University of Colorado, Aurora, CO

22. Retina Consultants, Hartford, CT

23. Helen and Harry Gray Cancer Center, Hartford, CT

24. Department of Ophthalmology, University of Alabama, Birmingham, AL

25. Tumori Foundation, San Francisco, CA

26. Department of Ophthalmology, University of Wisconsin, Madison, WI

27. Department of Ophthalmology, Emory University, Atlanta, GA

28. New England Eye Center and Department of Ophthalmology, Tufts University, Boston, MA

29. Colorado Retina Associates, Denver, CO

30. University of Texas MD Anderson Cancer Center, Houston, TX

31. Retinal Consultants Medical Group, Sacramento, CA

32. Retina Associates, Tucson, AZ

33. Department of Ophthalmology, Columbia University, New York, NY

34. O'Donnell School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX

Abstract

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 AND METHODS 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 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(+), 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(+). 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.

Publisher

American Society of Clinical Oncology (ASCO)

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