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.
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ICR Authors
Authors
Eggermont, AMM
Blank, CU
Mandala, M
Long, GV
Atkinson, VG
Dalle, S
Haydon, AM
Meshcheryakov, A
Khattak, A
Carlino, MS
Sandhu, S
Larkin, J
Puig, S
Ascierto, PA
Rutkowski, P
Schadendorf, D
Koornstra, R
Hernandez-Aya, L
Di Giacomo, AM
van den Eertwegh, AJM
Grob, J-J
Gutzmer, R
Jamal, R
Lorigan, PC
van Akkooi, ACJ
Krepler, C
Ibrahim, N
Marreaud, S
Kicinski, M
Suciu, S
Robert, C
Blank, CU
Mandala, M
Long, GV
Atkinson, VG
Dalle, S
Haydon, AM
Meshcheryakov, A
Khattak, A
Carlino, MS
Sandhu, S
Larkin, J
Puig, S
Ascierto, PA
Rutkowski, P
Schadendorf, D
Koornstra, R
Hernandez-Aya, L
Di Giacomo, AM
van den Eertwegh, AJM
Grob, J-J
Gutzmer, R
Jamal, R
Lorigan, PC
van Akkooi, ACJ
Krepler, C
Ibrahim, N
Marreaud, S
Kicinski, M
Suciu, S
Robert, C
Document Type
Journal Article
Date
2020-11-20
Date Accepted
Abstract
PURPOSE: We conducted the phase III double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. On the basis of 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, pembrolizumab prolonged RFS (hazard ratio [HR], 0.57; P < .0001) compared with placebo. This led to the approval of pembrolizumab adjuvant treatment by the European Medicines Agency and US Food and Drug Administration. Here, we report an updated RFS analysis at the 3.05-year median follow-up. PATIENTS AND METHODS: A total of 1,019 patients with complete lymph node dissection of American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7), stage IIIA (at least one lymph node metastasis > 1 mm), IIIB, or IIIC (without in-transit metastasis) cutaneous melanoma were randomly assigned to receive pembrolizumab at a flat dose of 200 mg (n = 514) or placebo (n = 505) every 3 weeks for 1 year or until disease recurrence or unacceptable toxicity. The two coprimary end points were RFS in the overall population and in those with programmed death-ligand 1 (PD-L1)-positive tumors. RESULTS: Pembrolizumab (190 RFS events) compared with placebo (283 RFS events) resulted in prolonged RFS in the overall population (3-year RFS rate, 63.7% v 44.1% for pembrolizumab v placebo, respectively; HR, 0.56; 95% CI, 0.47 to 0.68) and in the PD-L1-positive tumor subgroup (HR, 0.57; 99% CI, 0.43 to 0.74). The impact of pembrolizumab on RFS was similar in subgroups, in particular according to AJCC-7 and AJCC-8 staging, and BRAF mutation status (HR, 0.51 [99% CI, 0.36 to 0.73] v 0.66 [99% CI, 0.46 to 0.95] for V600E/K v wild type). CONCLUSION: In resected high-risk stage III melanoma, pembrolizumab adjuvant therapy provided a sustained and clinically meaningful improvement in RFS at 3-year median follow-up. This improvement was consistent across subgroups.
Citation
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2020, 38 (33), pp. 3925 - 3936
Source Title
Publisher
LIPPINCOTT WILLIAMS & WILKINS
ISSN
0732-183X
eISSN
1527-7755
Collections
Research Team
Melanoma and Kidney Cancer