Intraoperative ketorolac in high-risk breast cancer patients. A prospective, randomized, placebo-controlled clinical trial

Patrice Forget, Gauthier Bouche, Francois P Duhoux, Pierre G Coulie, Jan Decloedt, Alain Dekleermaker, Jean-Edouard Guillaume, Marc Ledent, Jean-Pascal Machiels, Véronique Mustin, Walter Swinnen, Aline van Maanen, Lionel Vander Essen, Jean-Christophe Verougstraete, Marc De Kock, Martine Berliere, Patrice Forget, Gauthier Bouche, Francois P Duhoux, Pierre G Coulie, Jan Decloedt, Alain Dekleermaker, Jean-Edouard Guillaume, Marc Ledent, Jean-Pascal Machiels, Véronique Mustin, Walter Swinnen, Aline van Maanen, Lionel Vander Essen, Jean-Christophe Verougstraete, Marc De Kock, Martine Berliere

Abstract

Background: Ketorolac 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.

Methods: The 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.

Findings: Between 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).

Conclusions: A 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 registration: ClinicalTrials.gov NCT01806259.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. CONSORT diagram.
Fig 1. CONSORT diagram.
Fig 2. Kaplan-Meier estimates of Disease-Free Survival…
Fig 2. Kaplan-Meier estimates of Disease-Free Survival (DFS) in the overall study population.
Fig 3. Kaplan-Meier estimates of Overall Survival…
Fig 3. Kaplan-Meier estimates of Overall Survival (OS) in the overall study population.

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