Abstract
BackgroundKetorolac has been associated with a lower risk of recurrence in retrospective studies, especially in patients with positive inflammatory markers. It is still unknown whether a single dose of pre-incisional ketorolac can prolong recurrence-free survival.MethodsThe KBC trial is a multicenter, placebo-controlled, randomized phase III trial in high-risk breast cancer patients powered for 33% reduction in recurrence rate (from 60 to 40%). Patients received one dose of ketorolac tromethamine or a placebo before surgery. Eligible patients were breast cancer patients, planned for curative surgery, and with a Neutrophil-to-Lymphocyte Ratio≥4, node-positive disease or a triple-negative phenotype. The primary endpoint was Disease-Free Survival (DFS) at two years. Secondary endpoints included safety, pain assessment and overall survival.FindingsBetween February 2013 and July 2015, 203 patients were assigned to ketorolac (n = 96) or placebo (n = 107). Baseline characteristics were similar between arms. Patients had a mean age of 55.7 (SD14) years.At two years, 83.1% of the patients were alive and disease free in the ketorolac vs. 89.7% in the placebo arm (HR: 1.23; 95%CI: 0.65–2.31) and, respectively, 96.8% vs. 98.1% were alive (HR: 1.09; 95%CI: 0.34–3.51).ConclusionsA single administration of 30 mg of ketorolac tromethamine before surgery does not increase disease-free survival in high risk breast cancer patients. Overall survival difference between ketorolac tromethamine group and placebo group was not statistically significant. The study was however underpowered because of lower recurrence rates than initially anticipated. No safety concerns were observed.Trial registrationClinicalTrials.gov NCT01806259.
Highlights
Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended to improve pain control in the perioperative period [1]
The biological effects of NSAIDs could be relevant to the perioperative period, as this period is marked by an activation of inflammatory pathways, which could contribute to accelerated tumor growth and dissemination [4, 5]
In the breast cancer studies, this association was noted in patients at high risk of early recurrence, i.e. related to tumor-related factors, signs of early dissemination and/or preoperative systemic inflammation as measured by the neutrophil-to-lymphocyte ratio (NLR) [3, 10, 12]
Summary
Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended to improve pain control in the perioperative period [1]. The biological effects of NSAIDs could be relevant to the perioperative period, as this period is marked by an activation of inflammatory pathways, which could contribute to accelerated tumor growth and dissemination [4, 5]. In both animal models [6, 7] and retrospective studies [3, 8], perioperative administration of NSAID has been associated with lower risk of cancer recurrence. It is still unknown whether a single dose of pre-incisional ketorolac can prolong recurrence-free survival
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