NGR-hTNF as second-line treatment in malignant pleural mesothelioma (MPM).

Abstract

7076 Background: NGR-hTNF exploits the asparagine-glycine-arginine (NGR) peptide for selectively targeting tumor necrosis factor (TNF) to cancer endothelial cells. Tumor hypervascularity is an independent predictor of poor overall survival (OS) in MPM patients (pts). Methods: We report long-term results of a phase II trial that assessed NGR-hTNF in MPM pts with performance status (PS) ≤ 2 and radiologic progressive disease (PD) after a pemetrexed-based regimen. NGR-hTNF was given at 0.8 µg/m2 every 3 weeks (q3w) in 43 pts and weekly (q1w) in 14 pts. Primary endpoint was progression free survival (PFS), with restaging done q6w by MPM-modified RECIST criteria, while secondary aims included disease control (DC) rate and OS. We also tested the impact on outcome of neutrophil to lymphocyte ratio (NLR) at baseline (median 3; interquartile range 2-5). Median follow-up was 32.5 months (95% CI 27.5-37.5). Results: Baseline characteristics were (n=57): median age 57 years; M/F 35/22; PS 0/1-2 31/26; EORTC score good/poor 45/12. Median treatment free interval on prior therapy was 4.3 months. Only one drug-related grade ≥ 3 adverse events (AEs) was noted, common grade 1/2 AEs being transient chills (75%). No higher toxicity was reported using the q1w schedule. Median PFS was 2.8 months (95% CI 2.2-3.3). DC rate was 46% (95% CI 32-59; 26/57 pts; 1 partial response, 25 stable diseases) and was maintained for a median time of 4.7 months (95% CI 4.0-5.4). OS rates at 1 and 2 years were 47% and 16%, respectively. Median OS was longer in pts with DC than in those with early PD (16.2 and 8.3 months, respectively; p=.02). According to schedule, 6-month PFS rates were 11% and 36% and 2-year OS rates were 12% and 29% for q3w and q1w, respectively. In pts with DC, median PFS were 4.4 and 9.1 months and median OS were 13.3 and 24.8 months for q3w and q1w, respectively. By Cox analyses, a PS of 0 (p=.01) and a low baseline NLR (p=.004) were the only variables associated with improved OS. Median OS in pts stratified by NLR ≤ 2, 3 to 4, and ≥ 5 were 15.7, 10.5, and 4.2 months, respectively (p=.0002 for trend). Conclusions: NGR-hTNF showed promising PFS and OS in this study. A double-blind phase III trial is currently testing best investigator choice ± NGR-hTNF q1w in pemetrexed-pretreated MPM pts (NCT01098266).