Project Description

Oral Abstract Presentation
Selected by the 2020 Annual Meeting Scientific Program Committee
Type: Oral Abstract Presentation
Presenter: Alexander M. Eggermont, MD, PhD, FASCO, BA
Presented: May 29, 2020
Abstract ref: 10000
Subtitles/Captions:

Authors: Alexander M. Eggermont, Christian U. Blank, Mario Mandalà, Georgina V. Long, Victoria Atkinson, Stéphane Dalle, Andrew Mark Haydon, Andrey Meshcheryakov, Muhammad Khattak, Matteo S. Carlino, Shahneen Kaur Sandhu, Susana Puig, Paolo Antonio Ascierto, Alexander Christopher Jonathan Van Akkooi, Clemens Krepler, Nageatte Ibrahim, Sandrine Marreaud, Michal Kicinski, Stefan Suciu, Caroline Robert; Princess Máxima Center, Utrecht, Netherlands; Netherlands Cancer Institute, Amsterdam, Netherlands; ASST Papa Giovanni XXIII, Bergamo, Italy; Melanoma Institute Australia, The University of Sydney, Royal North Shore Hospital, Mater Hospital, Sydney, Australia; University of Queensland, Brisbane, Australia; Hospices Civils de Lyon, Pierre-Bénite, France; The Alfred Hospital, Melbourne, VIC, Australia; NN Blokhin Cancer Research Center, Moscow, Russian Federation; Fiona Stanley Hospital/University of Western Australia, Perth, Australia; Westmead Hospital, Sydney, NSW, Australia; Peter MacCallum Cancer Centre, Melbourne, Australia; Hospital Clinic de Barcelona, Barcelona, Spain; Fondazione IRCCS-Istituto Nazionale dei Tumori, Naples, Italy; Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands; The Wistar Inst, Philadelphia, PA; Merck & Co., Inc., Kenilworth, NJ; EORTC Headquarters, Brussels, Belgium; Gustave Roussy and Paris-Saclay University, Villejuif, France

Abstract Disclosures

Research Funding: Merck

Background: We conducted the phase 3 double-blind EORTC 1325/KEYNOTE-054 trial to evaluate pembrolizumab vs placebo in patients (pts) with resected high-risk stage III melanoma. Based on 351 recurrence-free survival (RFS) events and at a median follow-up of 1.25 years (yrs), pembrolizumab improved 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.

Methods: 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). A total of 1019 pts were randomized (stratification by stage and region) 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 co-primary endpoints were RFS in the intention-to-treat overall population and in pts with PD-L1-positive tumors. Here, we report an updated RFS analysis based on a longer follow-up.

Results: Overall, 15%/46%/39% of pts had stage IIIA/IIIB/IIIC. At 3.05-yr median follow-up, pembrolizumab (190 RFS events) compared with placebo (283 RFS events) prolonged RFS, in the overall population and in the PD-L1 positive tumor subgroup (see Table). RFS was consistently prolonged across subgroups, in particular according to AJCC-7 staging, BRAF-V600 E/K mutation status.

Conclusions: Pembrolizumab, administered at 200 mg every 3 weeks for up to 1 year as adjuvant therapy, provided, at a 3-yr median follow-up, a sustained improvement in RFS, which was clinically meaningful, in resected high-risk stage III melanoma. This improvement was consistent across subgroups. In the overall population, the 3-yr cumulative incidence of distant metastasis being the first recurrence was 22.3% (pembrolizumab group) vs 37.3% (placebo group) (HR 0.55, 95% CI 0.44-0.69). Clinical trial information: NCT02362594

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Oral Abstract Presentation
Selected by the 2020 Annual Meeting Scientific Program Committee
Type: Oral Abstract Presentation
Presenter: Alexander M. Eggermont, MD, PhD, FASCO, BA
Presented: May 29, 2020
Abstract ref: 10000
Subtitles/Captions: