Seven-year analysis of adjuvant pembrolizumab versus placebo in stage III melanoma in the EORTC1325 / KEYNOTE-054 trial
Eggermont, Alexander MM; Kicinski, Michal; Blank, Christian U.; Mandala, Mario; Long, Georgina V.; Atkinson, Victoria; Dalle, Stéphane; Haydon, Andrew; Meshcheryakov, Andrey; Khattak, Adnan; Carlino, Matteo S.; Sandhu, Shahneen; Larkin, James; Puig, Susana; Ascierto, Paolo A.; Rutkowski, Piotr; Schadendorf, Dirk; Boers-Sonderen, Marye; Di Giacomo, Anna Maria; van den Eertwegh, Alfonsus JM; Grob, Jean Jacques; Gutzmer, Ralf; Jamal, Rahima; van Akkooi, Alexander C.J.; Lorigan, Paul; Grebennik, Dmitri; Kreplere, Clemens; Marreaud, Sandrine; Suciu, Stefan; Robert, Caroline
(2024) European Journal of Cancer, volume 211
(Article)
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
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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.
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Keywords: Adjuvant treatment, Anti-PD1, Anti-PDL1, Clinical trial, Immune checkpoint inhibitors, Immunotherapy, Melanoma, Pembrolizumab, Phase 3, Oncology, Cancer Research
ISSN: 0959-8049
Publisher: Elsevier Limited
Note: Publisher Copyright: © 2024
(Peer reviewed)