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
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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