Prognostic and predictive value of AJCC-8 staging in the phase III EORTC1325/KEYNOTE-054 trial of pembrolizumab vs placebo in resected high-risk stage III melanoma
Autor: | James Larkin, Ralf Gutzmer, Andrew Haydon, Paul Lorigan, Rutger H. T. Koornstra, Stéphane Dalle, Adnan Khattak, Alexander C.J. van Akkooi, Alfonsus J M van den Eertwegh, Christian U. Blank, Anna Maria Di Giacomo, Rahima Jamal, Clemens Krepler, Robert J. Lupinacci, Alexander M.M. Eggermont, Jean-Jacques Grob, Stefan Suciu, Leonel Hernandez-Aya, Caroline Robert, Matteo S. Carlino, Piotr Rutkowski, Nageatte Ibrahim, Mario Mandalà, Sandrine Marreaud, Georgina V. Long, Dirk Schadendorf, Paolo A. Ascierto, Michal Kicinski, Susana Puig, Victoria Atkinson, Shahneen Sandhu, Mikhail Lichinitser |
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Přispěvatelé: | Medical oncology, CCA - Cancer biology and immunology, CCA - Cancer Treatment and quality of life, AII - Cancer immunology |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Oncology Male Cancer Research Skin Neoplasms medicine.medical_treatment Medizin Pembrolizumab Metastasis Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2] 0302 clinical medicine Antineoplastic Agents Immunological Adjuvant therapy AJCC-7 AJCC-8 EORTC 1325/KN-054 Melanoma Phase III trial Predictive factors Prognostic factors Adult Aged Antibodies Monoclonal Humanized Disease-Free Survival Double-Blind Method Female Humans Middle Aged Neoplasm Staging Prognosis Treatment Outcome Monoclonal Humanized Hazard ratio Editorial Commentary Immunological 030220 oncology & carcinogenesis medicine.drug medicine.medical_specialty Antineoplastic Agents Ipilimumab Antibodies 03 medical and health sciences All institutes and research themes of the Radboud University Medical Center Internal medicine medicine business.industry Cancer medicine.disease 030104 developmental biology Lymphadenectomy business |
Zdroj: | Ann Transl Med European Journal of Cancer, 116, pp. 148-157 European Journal of Cancer, 116, 148-157. Pergamon Eggermont, A M M, Blank, C U, Mandala, M, Long, G V, Atkinson, V G, Dalle, S, Haydon, A, Lichinitser, M, Khattak, A, Carlino, M S, Sandhu, S, Larkin, J, Puig, S, Ascierto, P A, Rutkowski, P, Schadendorf, D, Koornstra, R, Hernandez-Aya, L, di Giacomo, A M, van den Eertwegh, A J M, Grob, J-J, Gutzmer, R, Jamal, R, Lorigan, P C, Lupinacci, R, Krepler, C, Ibrahim, N, Kicinski, M, Marreaud, S, van Akkooi, A C, Suciu, S & Robert, C 2019, ' Prognostic and predictive value of AJCC-8 staging in the phase III EORTC1325/KEYNOTE-054 trial of pembrolizumab vs placebo in resected high-risk stage III melanoma ', European Journal of Cancer, vol. 116, pp. 148-157 . https://doi.org/10.1016/j.ejca.2019.05.020 European Journal of Cancer, 116, 148-157 |
ISSN: | 0959-8049 |
Popis: | Background: The 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 results: Patients (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]). Conclusions: AJCC-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. |
Databáze: | OpenAIRE |
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