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

Alexander M M Eggermont ¹, Christian U Blank ², Mario Mandalà ³

¹Princess Máxima Center, Utrecht, Netherlands; University Medical Center Utrecht, Utrecht, Netherlands.
²Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, Netherlands.
³Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
⁴Melanoma Institute Australia, the University of Sydney, and Mater and Royal North Shore Hospitals, Sydney, NSW, Australia.
⁵Princess Alexandra Hospital, Brisbane, QLD, Australia.
⁶Hospices Civils de Lyon Cancer Institute, Lyon, France.
⁷Alfred Hospital, Melbourne, VIC, Australia.
⁸NN Blokhin Cancer Research Center, Moscow, Russia.
⁹Fiona Stanley Hospital & Edith Cowan University, Perth, WA, Australia.
¹⁰Westmead and Blacktown Hospitals, Melanoma Institute Australia and the University of Sydney, Sydney, NSW, Australia.
¹¹Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
¹²Royal Marsden Hospital, London, UK.
¹³Hospital Clinic de Barcelona, Universitat de Barcelona, Spain & Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, Barcelona, Spain.
¹⁴Istituto Nazionale Tumori IRCCS "Fondazione G Pascale", Naples, Italy.
¹⁵Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
¹⁶University Hospital Essen, Essen and German Cancer Consortium, Heidelberg, Germany.
¹⁷Radboud University Medical Center Nijmegen, Nijmegen, Netherlands.
¹⁸Washington University School of Medicine, St Louis, MO, USA.
¹⁹Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy.
²⁰Amsterdam University Medical Center, VUMC, Amsterdam, Netherlands.
²¹Aix Marseille University, Hôpital de la Timone, Marseille, France.
²²Skin Cancer Center, Hannover Medical School, Hannover, Germany.
²³Centre Hospitalier de l'Université de Montréal (CHUM), Centre de recherche du CHUM, Montreal, QC, Canada.
²⁴Christie NHS Foundation Trust, Manchester, UK.
²⁵Merck & Co, Kenilworth, NJ, USA.
²⁶EORTC Headquarters, Brussels, Belgium.
²⁷Gustave Roussy and Paris-Saclay University, Villejuif, France.

⁰Princess Máxima Center, Utrecht, Netherlands; University Medical Center Utrecht, Utrecht, Netherlands.

The Lancet. Oncology +

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April 15, 2021

View abstract on PubMed

Summary

Adjuvant pembrolizumab significantly improved distant metastasis-free survival in patients with resected high-risk stage III melanoma. This finding supports its use in preventing melanoma recurrence and spread.

Area Of Science

Oncology
Immunotherapy
Melanoma Research

Background

The EORTC 1325/KEYNOTE-054 trial investigated adjuvant pembrolizumab versus placebo for resected high-risk stage III melanoma.
Previous data showed improved recurrence-free survival (RFS) with pembrolizumab at 15-month follow-up, leading to regulatory approvals.
This report presents final results for distant metastasis-free survival (DMFS) and updated RFS data.

Purpose Of The Study

To report the final analysis of distant metastasis-free survival (DMFS) as a secondary endpoint.
To provide an updated analysis of recurrence-free survival (RFS) from the EORTC 1325/KEYNOTE-054 trial.
To evaluate the long-term efficacy of adjuvant pembrolizumab in high-risk stage III melanoma patients.

Main Methods

A double-blind, randomized, controlled phase 3 trial conducted across 123 centers in 23 countries.
Eligible patients with resected AJCC-7 stage IIIA, IIIB, or IIIC cutaneous melanoma received pembrolizumab (200 mg IV every 3 weeks for up to 18 doses) or placebo.
Randomization was stratified by stage and region; primary endpoints were RFS in the intention-to-treat (ITT) and PD-L1-positive populations.

Main Results

At a median follow-up of 42.3 months, 3.5-year DMFS was significantly higher with pembrolizumab (65.3%) versus placebo (49.4%) in the ITT population (HR 0.60; p<0.0001).
In PD-L1-positive patients, 3.5-year DMFS was 66.7% with pembrolizumab vs. 51.6% with placebo (HR 0.61; p<0.0001).
Updated RFS at 3.5 years also favored pembrolizumab in both ITT (59.8% vs. 41.4%) and PD-L1-positive (61.4% vs. 44.1%) populations.

Conclusions

Adjuvant pembrolizumab demonstrated a significant and clinically meaningful improvement in DMFS at 3.5-year follow-up.
These findings are consistent with the previously observed improvements in RFS.
The results strongly support the use of adjuvant pembrolizumab for patients with resected, high-risk stage III cutaneous melanoma.