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.

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/m(2) or pemetrexed 500 mg/m(2) 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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 2 Pg. 189-94 (Jan 10 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 25452446 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• Biomarkers, Tumor
• Glutamates
• Prostaglandins
• Pyrroles
• Sulfonamides
• Taxoids
• Pemetrexed
• Docetaxel
• apricoxib
• Guanine
• 7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid
• Cyclooxygenase 2
• PTGS2 protein, human

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (urine)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology, urine)
• Cyclooxygenase 2 (metabolism)
• Disease-Free Survival
• Docetaxel
• Double-Blind Method
• Drug Administration Schedule
• Female
• Glutamates (administration & dosage)
• Guanine (administration & dosage, analogs & derivatives)
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms (drug therapy, pathology, urine)
• Male
• Middle Aged
• Neoplasm Staging
• Patient Selection
• Pemetrexed
• Prostaglandins (urine)
• Pyrroles (administration & dosage, adverse effects)
• Sulfonamides (administration & dosage, adverse effects)
• Taxoids (administration & dosage)
• Treatment Outcome