No Benefit of COX-2 Inhibitor Apricoxib in Combination With Docetaxel or Pemetrexed in Second-line Treatment of Patients With Biomarker-Selected NSCLC
In a phase II study reported in the Journal of Clinical Oncology, Edelman et al found no benefit of adding the daily COX-2 inhibitor apricoxib to second-line docetaxel or pemetrexed (Alimta) in patients with non–small cell lung cancer (NSCLC) who exhibited suppressed levels of the urinary metabolite of prostaglandin E2 (PGE2) in response to apricoxib.
Overexpression of COX-2 is associated with advanced stage and worse outcomes in NSCLC, potentially as a result of elevated levels of COX-2-dependent PGE2. Some data suggest that COX-2 inhibitors produce better outcome in patients exhibiting suppression of the urinary metabolite of PGE2 (PGE-M) in response to COX-2 inhibition.
Study Details
Patients with NSCLC who had disease progression after one line of platinum-based therapy were eligible for the study, with only those exhibiting a ≥ 50% decrease in urinary PGE-M after 5 days of apricoxib treatment being enrolled. Patients received investigator-selected docetaxel at 75 mg/m2 or pemetrexed at 500 mg/m2 once every 21 days plus apricoxib at 400 mg daily or placebo. The primary endpoint was progression-free survival.
No Difference in Progression-Free Survival
Of the 101 patients who completed screening, 72 of 80 who demonstrated ≥ 50% suppression of PGE-M were randomly assigned to receive apricoxib (n = 36) or placebo (n = 36). Median progression-free survival was 85 days (95% confidence interval [CI] = 67–142 days) in the apricoxib group vs 97 days (95% CI = 52–193 days) in the placebo group (hazard ratio [HR] = 1.03, P = .91).
Median progression-free survival was 75 days in patients receiving docetaxel/apricoxib (n = 17) vs 97 days in those receiving docetaxel/placebo (n = 20; HR = 1.62, P = .18) and 103 days in those receiving pemetrexed/apricoxib (n = 19) vs 98 days in those receiving pemetrexed/placebo (n = 16; HR = 0.782, P = .49).
Median overall survival was 233 days in the apricoxib group and 287 days in the placebo group (P = .87).
Negative Marker
Baseline PGE-M was a negative prognostic marker for overall survival (P = .033) but not for progression-free survival, and an interaction between baseline PGE-M and chemotherapy was found for progression-free survival (P = .026). In patients receiving docetaxel, each unit increase in baseline urinary PGE-M increased the HR for progression-free survival by 1.014 (P = .038) and for overall survival by 1.015 (P = .033), whereas baseline PGE-M was not associated with progression-free or overall survival in patients receiving pemetrexed (P > .10).
Toxicity was similar in the two groups.
The investigators concluded: “Apricoxib did not improve [progression-free survival], despite biomarker-driven patient selection.”
Martin J. Edelman, MD, of University of Maryland Greenebaum Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
