KEY TAKEAWAYS
- The MK-3475-054/1325-MG/KEYNOTE-054 phase 3 trial aimed to investigate the association of NSAIDs with RFS, DMFS, and irAEs in high-risk patients with resected melanoma.
- Researchers noticed no significant associations between NSAIDs and efficacy outcomes or risk of irAEs in patients with resected high-risk stage III melanoma patients.
Pain management is crucial in cancer care, with NSAIDs recommended by the World Health Organisation. This study examines NSAIDs’ impact on survival and immune-related adverse events (irAEs) in high-risk resected melanoma patients from the EORTC 1325/KEYNOTE-054 trial.
Oliver John Kennedy and the team aimed to assess associations of NSAIDs with recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and the incidence of irAEs in this cohort.
Researchers performed an inclusive analysis on patients with AJCC7 stage IIIA, IIIB, or IIIC resected melanoma who were randomized to receive either 200 mg of adjuvant pembrolizumab (Pembro) (N = 514) or placebo (N = 505) every 3 weeks for one year or until recurrence.
As previously reported, Pembro prolonged RFS and DMFS. NSAID use, defined as administration between 7 days pre-randomization and treatment initiation, was evaluated. Multivariable Cox and Fine and Gray models were utilized to estimate hazard ratios (HRs) for associations of NSAIDs with RFS, DMFS, and irAEs.
About 1019 patients were randomized, with 59 and 44 patients in the Pembro and placebo arms, respectively, using NSAIDs. NSAIDs did not show association with recurrence-free survival (HR 0.91, 95% CI 0.58-1.43) or DMFS in either the Pembro (HR 1.03, 95% CI 0.65-1.66) or placebo arms (HR 0.76, 95% CI 0.48-1.20 for RFS; HR 0.80, 95% CI 0.49-1.31 for DMFS). However, NSAIDs were linked with increased incidence of irAEs in the placebo arm (HR 3.06, 95% CI 1.45-6.45) but not in the Pembro arm (HR 0.94, 95% CI 0.58-1.53).
The study concluded that NSAIDs did not show an association with efficacy outcomes or the risk of irAEs in patients with resected high-risk stage III melanoma receiving adjuvant Pembro.
The trial was sponsored by Merck Sharp & Dohme LLC
Source: https://pubmed.ncbi.nlm.nih.gov/38402687/
Clinical Trial: https://clinicaltrials.gov/study/NCT02362594
Kennedy OJ, Glassee N, Kicinski M, et al. (2024). “Prognostic and predictive value of non-steroidal anti-inflammatory drugs in the EORTC 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma.” Eur J Cancer. 2024 Apr;201:113585. doi: 10.1016/j.ejca.2024.113585. Epub 2024 Feb 1. PMID: 38402687.
