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

• Published in: European journal of cancer (1990) 2024-04, Vol.201, p.113585-113585, Article 113585
• Main Authors: Kennedy, Oliver John, Glassee, Nina, Kicinski, Michal, Blank, Christian U., Long, Georgina V., Atkinson, Victoria G., Dalle, Stéphane, Haydon, Andrew M., Meshcheryakov, Andrey, Khattak, Adnan, Carlino, Matteo S., Sandhu, Shahneen, Larkin, James, Puig, Susana, Ascierto, Paolo A., Rutkowski, Piotr, Schadendorf, Dirk, Boers-Sonderen, Marye, Giacomo, Anna Maria Di, van den Eertwegh, Alfonsus J.M., Grob, Jean-Jacques, Gutzmer, Ralf, Jamal, Rahima, van Akkooi, Alexander C.J., Gandini, Sara, Buhrer, Emanuel, Suciu, Stefan, Robert, Caroline, Eggermont, Alexander M.M., Mandala, Mario, Lorigan, Paul, Valpione, Sara
• Format: Article
• Language: English
• Subjects: Cyclooxygenase inhibitors; Immune checkpoint inhibitors; Immunotherapy; Melanoma; Non-steroidal anti-inflammatory drugs; Pembrolizumab
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2024.113585

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 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. 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). NSAIDs were not associated with efficacy outcomes nor the risk of irAEs in patients with resected high-risk stage III melanoma receiving adjuvant pembrolizumab. •NSAIDs were not associated with recurrence-free survival.•NSAIDs were not associated with distant metastasis-free survival.•NSAIDs were not associated with the incidence of immune-related adverse events.