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
- Author(s)
- Kennedy, OJ; Glassee, N; Kicinski, M; Blank, CU; 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; Boers-Sonderen, M; Giacomo, AMD; van den Eertwegh, AJM; Grob, JJ; Gutzmer, R; Jamal, R; van Akkooi, ACJ; Gandini, S; Buhrer, E; Suciu, S; Robert, C; Eggermont, AMM; Mandala, M; Lorigan, P; Valpione, S;
- Journal Title
- European Journal of Cancer
- Publication Type
- Research article
- Abstract
- BACKGROUND: Pain is common in patients with cancer. The World Health Organisation recommends paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) for mild pain and combined with other agents for moderate/severe pain. This study estimated associations of NSAIDs with recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and the incidence of immune-related adverse events (irAEs) in high-risk patients with resected melanoma in the EORTC 1325/KEYNOTE-054 phase III clinical trial. PATIENTS AND METHODS: Patients with AJCC7 stage IIIA, IIIB or IIIC resected melanoma were randomized to receive 200 mg of adjuvant pembrolizumab (N = 514) or placebo (N = 505) 3-weekly for one year or until recurrence. As previously reported, pembrolizumab prolonged RFS and DMFS. NSAID use was defined as administration between 7 days pre-randomization and starting treatment. Multivariable Cox and Fine and Gray models were used to estimate hazard ratios (HRs) for associations of NSAIDs with RFS, DMFS and irAEs. RESULTS: Of 1019 patients randomized, 59 and 44 patients in the pembrolizumab and placebo arms, respectively, used NSAIDs. NSAIDs were not associated with RFS (HR 0.91, 95% CI 0.58-1.43) or DMFS in the pembrolizumab (HR 1.03, 95% CI 0.65-1.66) or placebo arms (for RFS, HR 0.76, 95% CI 0.48-1.20; for DMFS, HR 0.80, 95% CI 0.49-1.31). NSAIDs were associated with the incidence of irAEs in the placebo arm (HR 3.06, 95% CI 1.45-6.45) but not in the pembrolizumab arm (HR 0.94, 95% CI 0.58-1.53). CONCLUSION: NSAIDs were not associated with efficacy outcomes nor the risk of irAEs in patients with resected high-risk stage III melanoma receiving adjuvant pembrolizumab.
- Publisher
- Elsevier
- Keywords
- Humans; *Melanoma/drug therapy/surgery/pathology; Prognosis; Neoplasm Staging; Disease-Free Survival; *Skin Neoplasms/drug therapy/surgery/pathology; Adjuvants, Immunologic/therapeutic use; Pain; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use; Anti-Inflammatory Agents/therapeutic use; *Antibodies, Monoclonal, Humanized; Cyclooxygenase inhibitors; Immune checkpoint inhibitors; Immunotherapy; Melanoma; Non-steroidal anti-inflammatory drugs; Pembrolizumab
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1016/j.ejca.2024.113585
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-07-11 01:47:34
Last Modified: 2024-07-11 01:48:11