TY - JOUR
T1 - Seven-year analysis of adjuvant pembrolizumab versus placebo in stage III melanoma in the EORTC1325 / KEYNOTE-054 trial
AU - Eggermont, Alexander Mm
AU - Kicinski, Michal
AU - Blank, Christian U
AU - Mandala, Mario
AU - Long, Georgina V
AU - Atkinson, Victoria
AU - Dalle, Stéphane
AU - Haydon, Andrew
AU - Meshcheryakov, Andrey
AU - Khattak, Adnan
AU - Carlino, Matteo S
AU - Sandhu, Shahneen
AU - Larkin, James
AU - Puig, Susana
AU - Ascierto, Paolo A
AU - Rutkowski, Piotr
AU - Schadendorf, Dirk
AU - Boers-Sonderen, Marye
AU - Di Giacomo, Anna Maria
AU - van den Eertwegh, Alfonsus Jm
AU - Grob, Jean-Jacques
AU - Gutzmer, Ralf
AU - Jamal, Rahima
AU - van Akkooi, Alexander C J
AU - Lorigan, Paul
AU - Grebennik, Dmitri
AU - Kreplere, Clemens
AU - Marreaud, Sandrine
AU - Suciu, Stefan
AU - Robert, Caroline
N1 - Copyright © 2024. Published by Elsevier Ltd.
PY - 2024/11
Y1 - 2024/11
N2 - UNLABELLED: In the previously reported primary analyses of this phase 3 trial, 12 months of adjuvant pembrolizumab resulted in significantly longer recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) than placebo in patients with resected high risk stage III melanoma. Stability of these benefits when the median follow-up was 3.5 and 5 years was published. Here we report results with a longer follow-up.METHODS: We randomized 1019 patients to receive pembrolizumab 200 mg or placebo, intravenously every 3 weeks for a total of 18 doses. RFS in the overall population and in the subgroup of patients with melanoma positive for the PD-1 ligand (PD-L1) were co-primary endpoints. DMFS in these two populations was a secondary and progression/recurrence-free survival 2 (PRFS2) an exploratory endpoint.RESULTS: The median follow-up was 6.9 years. In the overall intention-to-treat population, RFS was longer in the pembrolizumab group than in the placebo group (HR 0.63, 95 % CI 0.53 to 0.74). RFS at 7 years was 50 % (95 % CI 46 % to 55 %) in the pembrolizumab and 36 % (95 % CI 32 % to 41 %) in the placebo group. Positive effects were present both for loco-regional recurrences and distant metastases, and across substages IIIA-IIIB-IIIC, and PD-L1 positive and PD-L1 negative as well as for BRAF mutant and BRAF wild type populations. DMFS was longer in the pembrolizumab group than in the placebo group (HR 0.64, 95 % CI 0.54 to 0.76). DMFS at 7 years was 54 % (95 % CI 50 % to 59 %) in the pembrolizumab and 42 % (95 % CI 37 % to 46 %) in the placebo group. PRFS2 was longer in the pembrolizumab group than in the placebo group (HR 0.69, 95 % CI 0.57 to 0.84). PRFS2 at 7 years was 61 % (95 % CI 57 % to 66 %) in the pembrolizumab and 53 % (95 % CI 49 % to 57 %) in the placebo group.CONCLUSIONS: The 7-year analysis of adjuvant therapy with pembrolizumab demonstrated a sustained improvement in the long-term RFS, DMFS and PRFS2 compared with placebo in patients with resected stage III melanoma.
AB - UNLABELLED: In the previously reported primary analyses of this phase 3 trial, 12 months of adjuvant pembrolizumab resulted in significantly longer recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) than placebo in patients with resected high risk stage III melanoma. Stability of these benefits when the median follow-up was 3.5 and 5 years was published. Here we report results with a longer follow-up.METHODS: We randomized 1019 patients to receive pembrolizumab 200 mg or placebo, intravenously every 3 weeks for a total of 18 doses. RFS in the overall population and in the subgroup of patients with melanoma positive for the PD-1 ligand (PD-L1) were co-primary endpoints. DMFS in these two populations was a secondary and progression/recurrence-free survival 2 (PRFS2) an exploratory endpoint.RESULTS: The median follow-up was 6.9 years. In the overall intention-to-treat population, RFS was longer in the pembrolizumab group than in the placebo group (HR 0.63, 95 % CI 0.53 to 0.74). RFS at 7 years was 50 % (95 % CI 46 % to 55 %) in the pembrolizumab and 36 % (95 % CI 32 % to 41 %) in the placebo group. Positive effects were present both for loco-regional recurrences and distant metastases, and across substages IIIA-IIIB-IIIC, and PD-L1 positive and PD-L1 negative as well as for BRAF mutant and BRAF wild type populations. DMFS was longer in the pembrolizumab group than in the placebo group (HR 0.64, 95 % CI 0.54 to 0.76). DMFS at 7 years was 54 % (95 % CI 50 % to 59 %) in the pembrolizumab and 42 % (95 % CI 37 % to 46 %) in the placebo group. PRFS2 was longer in the pembrolizumab group than in the placebo group (HR 0.69, 95 % CI 0.57 to 0.84). PRFS2 at 7 years was 61 % (95 % CI 57 % to 66 %) in the pembrolizumab and 53 % (95 % CI 49 % to 57 %) in the placebo group.CONCLUSIONS: The 7-year analysis of adjuvant therapy with pembrolizumab demonstrated a sustained improvement in the long-term RFS, DMFS and PRFS2 compared with placebo in patients with resected stage III melanoma.
KW - Humans
KW - Melanoma/drug therapy
KW - Antibodies, Monoclonal, Humanized/therapeutic use
KW - Neoplasm Staging
KW - Skin Neoplasms/drug therapy
KW - Antineoplastic Agents, Immunological/therapeutic use
KW - Male
KW - Female
KW - Chemotherapy, Adjuvant
KW - Middle Aged
KW - Double-Blind Method
KW - Follow-Up Studies
KW - Aged
KW - B7-H1 Antigen/antagonists & inhibitors
KW - Adult
KW - Time Factors
U2 - 10.1016/j.ejca.2024.114327
DO - 10.1016/j.ejca.2024.114327
M3 - Article
C2 - 39288737
SN - 0959-8049
VL - 211
SP - 114327
JO - European journal of cancer (Oxford, England : 1990)
JF - European journal of cancer (Oxford, England : 1990)
ER -
