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Proffered Paper - Melanoma and other skin tumours

LBA46 - Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: Final results regarding distant metastasis-free survival from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial


19 Sep 2020


Proffered Paper - Melanoma and other skin tumours



Tumour Site



Alexander Eggermont


Annals of Oncology (2020) 31 (suppl_4): S1142-S1215. 10.1016/annonc/annonc325


A.M.M. Eggermont1, C.U. Blank2, M. Mandala'3, G.V. Long4, V. Victoria Atkinson5, S. Dalle6, A.M. Haydon7, A. Meshcheryakov8, A. Khattak9, M. Carlino10, S. Sandhu11, S. Puig Sarda12, P.A. Ascierto13, A.C.J. van Akkooi14, C. Krepler15, N. Ibrahim15, S.I. Marreaud16, M. Kicinski17, S. Suciu17, C. Robert18

Author affiliations

  • 1 Board Of Directors, Princess Máxima Center, 3584 CS - Utrecht/NL
  • 2 Medical Oncology Dept, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), 1066 CX - Amsterdam/NL
  • 3 Haemato-oncological, Azienda Ospedaliera Papa Giovanni XXIII, 24127 - Bergamo/IT
  • 4 Melanoma, Melanoma Institute Australia, 2065 - Wollstonecraft/AU
  • 5 Dermatology, University of Queensland, Brisbane/AU
  • 6 Dermatology, Lyon Sud Hospital Center, 69495 - Pierre Benite/FR
  • 7 Medical Oncology, Alfred Hospital, 3004 - Melbourne/AU
  • 8 Dermatology, N.N. Blokhin National Medical Research Center of Oncology, 115478 - Moscow/RU
  • 9 Dermatology, Fiona Stanley Hospital, 6150 - Murdoch/AU
  • 10 Dermatology, The Crown Princess Mary Cancer Centre, 2145 - Westmead/AU
  • 11 Medical Oncology, Peter MacCallum Cancer Centre, Melbourne/AU
  • 12 Dermatology, Hospital Clinic y Provincial de Barcelona, 08036 - Barcelona/ES
  • 13 Melanoma, Cancer Immunotherapy And Development Therapeutics Unit, Istituto Nazionale Tumori - IRCCS - Fondazione Pascale, 80131 - Napoli/IT
  • 14 Surgical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 15 Oncology, Merck & Co., Inc., Kenilworth/US
  • 16 Medical, EORTC - European Organisation for Research and Treatment of Cancer, 1200 - Brussels/BE
  • 17 Statistics, European Organisation for Research and Treatment of Cancer, 1200 - Brussels/BE
  • 18 Dermatology Department, Institut Gustave Roussy, 94805 - Villejuif/FR


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Abstract LBA46


We conducted the randomized phase III double-blind EORTC 1325/KEYNOTE-054 trial to evaluate pembrolizumab vs placebo in patients (pts) with resected high-risk stage III melanoma. At a 1.25-year (yr) median follow-up, pembrolizumab improved recurrence-free survival (RFS) (hazard ratio [HR] 0.57, P<0.0001) as compared to placebo (Eggermont, NEJM 2018). This led to the approval of pembrolizumab adjuvant treatment by EMA and FDA.


Eligible pts included those ≥18 yrs of age with complete resection of cutaneous melanoma metastatic to lymph node(s), classified as AJCC-7 stage IIIA (at least one lymph node metastasis >1 mm), IIIB or IIIC (without in-transit metastasis). Between Aug-2015 until Nov-2016, 1019 pts were randomized to pembrolizumab at a flat dose of 200 mg (N=514) or placebo (N=505) every 3 weeks for a total of 18 doses (∼1 year) or until disease recurrence or unacceptable toxicity. The 2 main co-primary endpoints were RFS in the intention-to-treat (ITT) overall population and in pts with PD-L1-positive tumors. Secondary endpoints included distant metastasis-free survival (DMFS) in these 2 respective populations. The final DMFS analysis was foreseen when approximately 423 DMFS events (distant metastases or deaths) are reported (∼87% power to detect a HR of 0.725 in the overall population).


By April 2020, 418 DMFS events were reported. At 3.5 yr median follow-up, pembrolizumab compared with placebo significantly prolonged DMFS in the overall population (3.5-yr DMFS rate: 65.3% vs 49.4%; HR 0.60, 95% CI 0.49-0.73; P<0.0001) and in the PD-L1-positive tumor (N=853; HR 0.61; 95% CI 0.49-0.76; P<0.0001). The impact of pembrolizumab on DMFS was similar in pts with a PD-L1-negative tumor (N=116; HR 0.49, 99% CI 0.24-0.99) and in other subgroups, in particular according to AJCC-7 and -8 staging, and BRAF mutation status. The RFS improvement was confirmed (HR in the ITT population 0.59; 95% CI 0.49-0.70).


At 3.5-yr median follow-up, pembrolizumab adjuvant therapy provided a clinically meaningful improvement in DMFS in resected high-risk stage III melanoma pts.

Clinical trial identification

EudraCT: 2014-004944-37.

Editorial acknowledgement

Legal entity responsible for the study

Merck & Co., Inc.


Merck & Co., Inc.


A.M.M. Eggermont: Honoraria (self): Biocad; Honoraria (self): BioInvent; Honoraria (self): BMS; Honoraria (self): Ellipses Pharma; Honoraria (self): GSK; Honoraria (self): HalioDx; Honoraria (self): IO Biotech; Honoraria (self): MedImmune; Honoraria (self): MSD; Honoraria (self): Nektar Therapeutics; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Regeneron Pharmaceuticals; Honoraria (self): Sanofi; Honoraria (self): Sallas Life Sciences. C.U. Blank: Honoraria (institution): MSD; Honoraria (institution): BMS; Honoraria (institution): Roche; Honoraria (institution): Novartis; Honoraria (institution): Pfizer; Honoraria (institution): Lilly; Honoraria (institution): GSK. M. Mandala': Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Pierre Fabre; Research grant/Funding (institution): Genentech/Roche. G.V. Long: Honoraria (self): Aduro; Honoraria (self): Amgen; Honoraria (self): Array BioPharma; Honoraria (self): BMS; Honoraria (self): Merck; Honoraria (self): Novartis; Honoraria (self): OncoSec. V. Victoria Atkinson: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck Serano; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: OncoSec; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche. S. Dalle: Shareholder/Stockholder/Stock options, Spouse/Financial dependant: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Travel/Accommodation/Expenses: Pierre Fabre. A.M. Haydon: Honoraria (self): Merck. A. Meshcheryakov: Advisory/Consultancy: Lilly Pharma; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck; Advisory/Consultancy: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Biocad; Travel/Accommodation/Expenses: Servier; Travel/Accommodation/Expenses: Merck Serono; Travel/Accommodation/Expenses: Lilly Pharma. A. Khattak: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD. M. Carlino: Honoraria (self): Amgen; Honoraria (self): BMS; Honoraria (self): Ideaya Biosciences; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Roche. S. Sandhu: Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Endocyte; Research grant/Funding (institution): MSD. S. Puig Sarda: Advisory/Consultancy: Isdin; Advisory/Consultancy, Research grant/Funding (institution): Leo Pharma; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Almirall; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Sanofi; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bioderma; Speaker Bureau/Expert testimony: La Roche Posay; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Pierre Fabre; Research grant/Funding (institution): Castle Bioscience; Research grant/Funding (institution): AMLO Bioscience; Research grant/Funding (institution): Melagenics. P.A. Ascierto: Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Array BioPharma; Advisory/Consultancy: Merck Serano; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Newlink Genetics; Advisory/Consultancy: Genmab; Advisory/Consultancy: Incyte; Advisory/Consultancy: MedImmune; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Syndax; Advisory/Consultancy: Sun Pharma; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Idera; Advisory/Consultancy: Ultimovacs; Advisory/Consultancy: Sandoz; Advisory/Consultancy: Immunocore; Advisory/Consultancy: 4SC; Advisory/Consultancy: Alkermes; Advisory/Consultancy: Italfarmaco. A.C.J. van Akkooi: Honoraria (institution), Research grant/Funding (institution): Amgen; Honoraria (institution), Research grant/Funding (institution): BMS; Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution), Research grant/Funding (institution): MSD; Honoraria (institution), Research grant/Funding (institution): Pfizer; Honoraria (institution), Research grant/Funding (institution): Sanofi; Honoraria (institution), Research grant/Funding (institution): 4SC. C. Krepler: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck. N. Ibrahim: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck; Shareholder/Stockholder/Stock options: GSK. M. Kicinski: Research grant/Funding (institution): MSD. S. Suciu: Research grant/Funding (institution): MSD. C. Robert: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Amgen; Advisory/Consultancy: Biothera; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: CureVac. All other authors have declared no conflicts of interest.

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