The KeyNote-054 (EORTC 1325-MG) Trial in Melanoma

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • The KEYNOTE-054 (EORTC 1325-MG) trial:
    • Was a double-blind, randomized, phase 3 study:
      • Evaluating adjuvant pembrolizumab (200 mg IV every 3 weeks for up to 1 year) versus placebo:
        • In patients with completely resected, high-risk stage III cutaneous melanoma
  • The trial demonstrated that adjuvant pembrolizumab:
    • Significantly improved recurrence-free survival (RFS) compared to placebo:
      • With a 3-year RFS rate of 63.7% for pembrolizumab versus 44.1% for placebo (hazard ratio [HR] 0.56, 95% CI 0.47–0.68)
    • This benefit was consistent across subgroups, including:
      • BRAF-mutant and wild-type melanoma, and regardless of PD-L1 status
    • Long-term follow-up (median 6.9 years) confirmed the durability of benefit:
      • With 7-year RFS of 50% for pembrolizumab versus 36% for placebo (HR 0.63, 95% CI 0.53–0.74)
    • Distant metastasis-free survival (DMFS) was also improved:
      • 7-year DMFS:
        • 54% vs 42%; HR 0.64, 95% CI 0.54–0.76
    • The safety profile was favorable:
      • With grade 3 to 4 adverse events in 14% of pembrolizumab-treated patients, and no significant long-term impact on health-related quality of life
  • In the context of current management:
    • These results establish adjuvant pembrolizumab as a standard of care for resected high-risk stage III melanoma:
      • Reducing both local and distant recurrence risk
  • For local recurrence after adjuvant therapy:
    • Management is multidisciplinary, and the benefit of rechallenge with anti–PD-1 therapy depends on timing and prior response
  • References:
    • Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-Mg/Keynote-054 Trial.
    • Eggermont AMM, Blank CU, Mandala M, et al. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2020;38(33):3925-3936. doi:10.1200/JCO.20.02110.
      Adjuvant Pembrolizumab Versus Placebo in Resected Stage III Melanoma (EORTC 1325-Mg/Keynote-054): Distant Metastasis-Free Survival Results From a Double-Blind, Randomised, Controlled, Phase 3 Trial. Eggermont AMM, Blank CU, Mandalà M, et al. The Lancet. Oncology. 2021;22(5):643-654. doi:10.1016/S1470-2045(21)00065-6.
    • Seven-Year Analysis of Adjuvant Pembrolizumab Versus Placebo in Stage III Melanoma in the EORTC1325 / KEYNOTE-054 Trial. Eggermont AM, Kicinski M, Blank CU, et al. European Journal of Cancer (Oxford, England : 1990). 2024;211:114327. doi:10.1016/j.ejca.2024.114327.
    • Adjuvant Pembrolizumab Versus Placebo in Resected Stage III Melanoma (EORTC 1325-Mg/Keynote-054): Health-Related Quality-of-Life Results From a Double-Blind, Randomised, Controlled, Phase 3 Trial. Bottomley A, Coens C, Mierzynska J, et al. The Lancet. Oncology. 2021;22(5):655-664. doi:10.1016/S1470-2045(21)00081-4.
    • Adjuvant Pembrolizumab Versus Placebo in Resected Stage III Melanoma (EORTC 1325-Mg/Keynote-054): Long-Term, Health-Related Quality-of-Life Results From a Double-Blind, Randomised, Controlled, Phase 3 Trial. Bührer E, Kicinski M, Mandala M, et al. The Lancet. Oncology. 2024;25(9):1202-1212. doi:10.1016/S1470-2045(24)00338-3.
    • Recent Advances in the Treatment of Melanoma. Curti BD, Faries MB. The New England Journal of Medicine. 2021;384(23):2229-2240. doi:10.1056/NEJMra2034861.
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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