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.

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.

Value of repeated measurements of lipoprotein (a) to assess cardiovascular risk: a retrospective study.

Background: High plasma concentrations of lipoprotein (a) [Lp(a)] are associated with an increased cardiovascular risk. Current guidelines recommend measurement of only a single Lp(a) in an individual's lifetime under specific circumstances to improve cardiovascular risk prediction. Accordingly, the question raised is the number of false positives and negatives missed through only a single measurement.Methods: All Lp(a) measurements between 2004 and March 2021 were retrieved from the laboratory database of the Erasme hospital. Only patients with repeated measurement were included. The first and subsequent Lp(a) measurement were compared. Two different cohorts were studied as a result of a change in Lp(a) determination methodology (n = 2049 and n = 309, respectively). The effects of a third Lp(a) measurement were assessed through binary analyses (n = 678). The 180 mg/dl (430 nmol/L) threshold recommended in the ESC guidelines was assessed first. Analysis was repeated for 100, 70 and 50 mg/dl thresholds of raised Lp(a) levels.Results: A low rate of false negatives (0.8%-1%) and false positives (0.6-0.3%) were revealed with two Lp(a) measurements. There was no difference in regards to the divergent Lp(a) thresholds nor the measurement of Lp(a) on two or three occasions.Conclusion: The present study showed Lp(a) determination to be reproducible. A single measurement is sufficient to assess if a patient exceeds various cut-off values of elevated Lp(a) levels.