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

PLoS One. 2019 Dec 4;14(12):e0225748. doi: 10.1371/journal.pone.0225748. eCollection 2019.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Belgium
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / pathology*
  • Female
  • Humans
  • Intraoperative Care*
  • Kaplan-Meier Estimate
  • Ketorolac / administration & dosage*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Recurrence
  • Retrospective Studies
  • Risk Assessment

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Ketorolac

Associated data

  • ClinicalTrials.gov/NCT01806259

Grants and funding

This work is financed by grants received by PF, in the name of his institution: the Anticancer Fund (no grant number) (www.anticancerfund.org); the Belgian Society of Anaesthesia and Resuscitation (no grant number) (www.sarb.be); the Fondation Saint-Luc (no grant number) (www.uclouvain.be); the Commission du Patrimoine of the Université catholique de Louvain, St-Luc Hospital (exceptional grant, no number) (www.uclouvain.be). None of the funders had any role in the study design, data collection and analysis, decision to publish or preparation of the manuscript except the scientific advise of GB, scientific director of the Anticancer Fund.