Oral Presentation ASDR Annual Scientific Meeting 2019

Prognostic/predictive value of AJCC-8 staging in the phase 3 EORTC-1325/KEYNOTE-054 trial: pembrolizumab vs placebo in resected high-risk stage III melanoma (#5)

Alexander M. Eggermont 1 , Christian Blank 2 , Mario Mandala 3 , Georgina V. Long 4 , Victoria G. Atkinson 5 , Stéphane Dalle 6 , Andrew Haydon 7 , Mikhail Lichinitser 8 , Adnan Khattak 9 , Matteo S. Carlino 10 , Shahneen Sandhu 11 , James Larkin 12 , Susana Puig 13 , Paolo A. Ascierto 14 , Piotr Rutkowski 15 , Dirk Schadendorf 16 , Rutger Koornstra 17 , Leonel Hernandez-Aya 18 , Michele Maio 19 , Alfonsus JM van den Eertwegh 20 , Jean-Jacques Grob 21 , Ralf Gutzmer 22 , Rahima Jamal 23 , Paul C. Lorigan 24 , Robert Lupinacci 25 , Clemens Krepler 25 , Nageatte Ibrahim 25 , Michal Kicinski 26 , Sandrine Marreaud 26 , Alexander C. van Akkooi 2 , Stefan Suciu 26 , Caroline Robert 1
  1. Gustave Roussy Cancer Campus Grand Paris, Villejuif, France
  2. Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, Netherlands
  3. Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
  4. Melanoma Institute Australia, the University of Sydney, and Mater and Royal North Shore Hospitals, Sydney, NSW, Australia
  5. Princess Alexandra Hospital, Brisbane, QLD, Australia
  6. Hospices Civils de Lyon Cancer Institute, Lyon, France
  7. Alfred Hospital, Melbourne, QLD, Australia
  8. Russian Oncology Scientific Centre, Moscow, Russian Federation
  9. Fiona Stanley Hospital/University of Western Australia, Perth, WA, Australia
  10. Westmead and Blacktown Hospitals, Melanoma Institute Australia and the University of Sydney, Sydney, Sydney, NSW, Australia
  11. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  12. Royal Marsden Hospital, London, United Kingdom
  13. Hospital Clinic Universitari de Barcelona, Barcelona, Spain
  14. Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Naples, Italy
  15. Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland
  16. Universitaetsklinikum – University Essen, Essen, Germany
  17. Radboud University Medical Center Nijmegen, Nijmegen, Netherlands
  18. Washington University School of Medicine, St. Louis, MO, USA
  19. Universita Degli Studi Di Siena -Policlinico "le Scotte", Siena, Italy
  20. VU University medical center, Amsterdam, Netherlands
  21. Aix Marseille University, Hôpital de la Timone, Marseille, France
  22. Skin Cancer Center, Hannover Medical School, Hannover, Germany
  23. Centre Hospitalier de l'Université de Montréal (CHUM), Centre de recherche du CHUM, Montreal, QC, Canada
  24. Christie NHS Foundation Trust, Manchester, United Kingdom
  25. Merck & Co., Inc., Kenilworth, NJ, USA
  26. EORTC HQ, Brussels, Belgium

The AJCC-8 classification of melanoma was implemented in January 2018. It was based on data gathered when checkpoint inhibitors were not used as adjuvant therapy in stage III melanoma. The EORTC-1325/KEYNOTE-054 double-blind phase 3 trial evaluated pembrolizumab vs placebo in AJCC-7 stage IIIA (excluding lymph node metastasis ≤1 mm), IIIB or IIIC (without in-transit metastasis) patients (pts) after complete resection of involved lymph node(s). Patients (n=1019) were randomized 1:1 to pembrolizumab 200 mg or placebo every 3 weeks (total of 18 doses, ~1 year). At 1.25 yr median follow-up, pembrolizumab prolonged relapse-free survival (RFS) in the total population (1-year RFS rate: 75.4% vs 61.0%; HR 0.57, 98.4% CI 0.43-0.74; P<0.0001), and the PD-L1-positive subgroup, and consistently in the AJCC-7 subgroups (Eggermont et al, NEJM, 2018). Prognostic and predictive values of AJCC-8 for RFS were evaluated in this trial. Patient distribution according to the AJCC-8 stage III subgroups was 8% (IIIA), 34.7% (IIIB), 49.7% (IIIC), 3.7% (IIID), and 3.8% (unknown). AJCC-8 classification was strongly associated with RFS (HRs for stage IIIB, IIIC, and IIID vs IIIA were 4.0, 5.6, and 12.1, respectively) but showed no predictive importance for the treatment comparison regarding RFS (test for interaction: P=0.68). The 1-year RFS rate for pembrolizumab vs placebo and the HRs (99% CI) within each AJCC-8 subgroup were: stage IIIA [92.7% vs 92.5%; 0.76 (0.11-5.43)], IIIB [79.0% vs 65.5%; 0.59 (0.35-0.99)], IIIC [73.6% vs 53.9%; 0.48 (0.33-0.70)], IIID [50.0% vs 33.3%; 0.69 (0.24-2.00)]. In this re-analysis, AJCC-8 had a strong prognostic importance for RFS, but no predictive importance: the RFS benefit of pembrolizumab was observed across AJCC-8 subgroups in resected high-risk stage III melanoma patients.

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