• Eggermont Alexander M M AMM Gustave Roussy Cancer Campus Grand Paris, Villejuif, France. Electronic address: alexander.eggermont@gustaveroussy.fr., Christian U Blank, Mario Mandala, Georgina V Long, Victoria G Atkinson, Stéphane Dalle, Andrew Haydon, Mikhail Lichinitser, Adnan Khattak, Matteo S Carlino, Shahneen Sandhu, James Larkin, Susana Puig, Paolo A Ascierto, Piotr Rutkowski, Dirk Schadendorf, Rutger Koornstra, Leonel Hernandez-Aya, Anna Maria Di Giacomo, Alfonsus Jm van den Eertwegh, Jean-Jacques Grob, Ralf Gutzmer, Rahima Jamal, Paul C Lorigan, Robert Lupinacci, Clemens Krepler, Nageatte Ibrahim, Michal Kicinski, Sandrine Marreaud, Alexander C van Akkooi, Stefan Suciu, and Caroline Robert.
• Gustave Roussy Cancer Campus Grand Paris, Villejuif, France. Electronic address: alexander.eggermont@gustaveroussy.fr.
• Eur. J. Cancer. 2019 Jul 1; 116: 148-157.

BackgroundThe American Joint Committee on Cancer-8 (AJCC) 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 European Organization for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 double-blind phase III trial evaluated pembrolizumab vs placebo in AJCC-7 stage IIIA (excluding lymph node metastasis ≤1 mm), IIIB or IIIC (without in-transit metastasis) patients after complete lymphadenectomy.Patients, Methods And ResultsPatients (n = 1019) were randomised 1:1 to pembrolizumab 200 mg or placebo every 3 weeks (total of 18 doses, ∼1 year). At 1.25-year median follow-up, pembrolizumab prolonged relapse-free survival (RFS) in the total population (1-year RFS rate: 75.4% vs 61.0%; hazard ratio [HR] 0.57; logrank P < 0.0001) and consistently in the AJCC-7 subgroups. Prognostic and predictive values of AJCC-8 for RFS were evaluated in this study. Patient distribution according to the AJCC-8 stage 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, 5.7 and 12.2, 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% confidence interval) within each AJCC-8 subgroup were as follows: 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]) and IIID (50.0% vs 33.3%; 0.69 [0.24-2.00]).ConclusionsAJCC-8 staging 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.Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.

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