Seven-year analysis of adjuvant pembrolizumab versus placebo in stage III melanoma in the EORTC1325 / KEYNOTE-054 trial
- Author(s)
- Eggermont, AM; Kicinski, M; Blank, CU; Mandala, M; Long, GV; Atkinson, V; Dalle, S; Haydon, A; Meshcheryakov, A; Khattak, A; Carlino, MS; Sandhu, S; Larkin, J; Puig, S; Ascierto, PA; Rutkowski, P; Schadendorf, D; Boers-Sonderen, M; Di Giacomo, AM; van den Eertwegh, AJ; Grob, JJ; Gutzmer, R; Jamal, R; van Akkooi, ACJ; Lorigan, P; Grebennik, D; Kreplere, C; Marreaud, S; Suciu, S; Robert, C;
- Journal Title
- European Journal of Cancer
- Abstract
- 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.
- Keywords
- Adjuvant treatment; Anti-PD1; Anti-PDL1; Clinical trial; Immune checkpoint inhibitors; Immunotherapy; Melanoma; Pembrolizumab; Phase 3
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1016/j.ejca.2024.114327
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- Refer to copyright notice on published article.
Creation Date: 2024-09-26 03:27:26
Last Modified: 2024-09-26 03:32:37