Randomized, double-blind, placebo-controlled, multicenter phase ii study of the efficacy and safety of apricoxib in combination with either docetaxel or pemetrexed in patients with biomarker-selected non-small-cell lung cancer

Martin J. Edelman, Ming T. Tan, Mary J. Fidler, Rachel E. Sanborn, Greg Otterson, Lecia V. Sequist, Tracey L. Evans, Bryan J. Schneider, Roger Keresztes, John S. Rogers, Jorge Antunez De Mayolo, Josephine Feliciano, Yang Yang, Michelle Medeiros, Sara L. Zaknoen

Research output: Contribution to journalArticle

Abstract

Purpose Overexpression of COX-2 correlates with advanced stage and worse outcomes in non-small-cell lung cancer (NSCLC), possibly as a result of elevated levels of COX-2-dependent prostaglandin E2 (PGE2). Exploratory analyses of studies that used COX-2 inhibitors have demonstrated potentially superior outcome in patients in whom the urinary metabolite of PGE2 (PGE-M) is suppressed. We hypothesized that patients with disease defined by PGE-M suppression would benefit from the addition of apricoxib to second-line docetaxel or pemetrexed. Patients and Methods Patients with NSCLC who had disease progression after one line of platinum-based therapy, performance status of 0 to 2, and normal organ function were potentially eligible. Only patients with a 50% decrease in urinary PGE-M after 5 days of treatment with apricoxib could enroll. Docetaxel 75 mg/m2 or pemetrexed 500 mg/m2 once every 21 days per the investigator was administered with apricoxib or placebo 400 mg once per day. The primary end point was progression-free survival (PFS). Exploratory analysis was performed regarding baseline urinary PGE-M and outcomes. Results In all, 101 patients completed screening, and 72 of the 80 who demonstrated 50% suppression were randomly assigned to apricoxib or placebo. Toxicity was similar between the arms. No improvement in PFS was seen with apricoxib versus placebo. The median PFS for the control arm was 97 days (95% CI, 52 to 193 days) versus 85 days (95% CI, 67 to 142 days) for the experimental arm (P =.91). Conclusion Apricoxib did not improve PFS, despite biomarker-driven patient selection.

Original languageEnglish (US)
Pages (from-to)189-194
Number of pages6
JournalJournal of Clinical Oncology
Volume33
Issue number2
DOIs
StatePublished - Oct 10 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Edelman, M. J., Tan, M. T., Fidler, M. J., Sanborn, R. E., Otterson, G., Sequist, L. V., Evans, T. L., Schneider, B. J., Keresztes, R., Rogers, J. S., De Mayolo, J. A., Feliciano, J., Yang, Y., Medeiros, M., & Zaknoen, S. L. (2015). Randomized, double-blind, placebo-controlled, multicenter phase ii study of the efficacy and safety of apricoxib in combination with either docetaxel or pemetrexed in patients with biomarker-selected non-small-cell lung cancer. Journal of Clinical Oncology, 33(2), 189-194. https://doi.org/10.1200/JCO.2014.55.5789