A randomized, double-blind, placebo-controlled multicenter phase II study of the COX-2 inhibitor apricoxib (A) in combination with either docetaxel (doc) or pemetrexed (pem) in advanced non-small cell lung cancer (NSCLC) patients (pts) selected by urinary PGE-m suppression.

Abstract

7546 Background: Overexpression of COX-2 has been associated with advanced stage and worse outcomes in NSCLC, possibly due to elevated levels of the COX-2 dependent prostaglandin, PGE-2. COX-2 inhibitors in addition to standard therapy has been associated with superior outcome in pts in whom the urinary metabolite of PGE-2, PGE-M is suppressed by the inhibitor. We hypothesized that pts defined by PGE-M suppression would benefit from the addition of apr to doc or pem. Methods: Pts with NSCLC, progressive after one platinum based therapy, PS 0-1, normal organ function, alb ≥2.5, CCr ≥ 45 were eligible for screening. A 5 day run in period with apr 400mg qd was performed. Only pts with a ≥ 50% decrease in urinary PGE-M could actually enroll. Chemotherapy was doc 75 mg/m2 or pem 500 mg/m2 q21 d per the investigator plus apr/placebo (P) 400 mg qd. The primary endpoint was progression free survival (PFS). Results: A total of 109 pts were screened of whom 72 demonstrated ≥50% suppression and enrolled (table). Toxicity was similar between the arms. No improvement in PFS was seen with apricoxib vs. placebo. By chemotherapy assignment: pem/apr vs. pem/P : 103 days vs. 98 (p =.49); doc/apr vs. doc/P: 75 vs. 97 (p=.18). An adverse interaction between baseline PGE-M and doc was seen in survival (p=.026); each unit increase in urinary PGE-M increased the HR by 1.014 (p < 0.038 ) vs. pem (HR =.990, p=n.s.). There was no correlation between baseline PGE-M or magnitude of PGE-M suppression and benefit from apr. Conclusions: 1. Apr did not improve outcome despite patient selection. 2. There was a trend towards an adverse outcome when apr was combined with docetaxel, that was not evident with pemetrexed. 3. Baseline urinary PGE-M may be an adverse prognostic factor for treatment with doc. [Table: see text]