NGR-hTNF in previously treated patients with malignant pleural mesothelioma (MPM) .

Abstract

7089 Background: NGR-hTNF exploits the tumor-homing peptide NGR for selectively targeting tumor necrosis factor to tumor blood vessels. Methods: Here we report the long-term results of a phase II trial testing NGR-hTNF in 57 MPM patients (pts) who had failed a pemetrexed-based regimen. NGR-hTNF was given as 1-hour infusion at 0.8 µg/m2 every 3 weeks (q3w; n=43) or weekly (q1w; n=14) in a subsequent cohort. Moreover, we assessed the impact on outcome of the systemic neutrophil-to-lymphocyte ratio (NLR), an index of the host immune response to tumor. Median baseline NLR was 3 (range 1-23). Results: In the whole study population (n=57), one grade 3 drug-related toxicity was observed and common grades 1-2 were transient chills (75% of pts). There was no higher toxicity using the q1w schedule. Median progression-free survival (PFS) was 2.8 months (95% CI 2.2-3.3). The disease control rate was 46% (26/57 pts; 95% CI 33-60%) and was maintained for a median time of 4.7 months (95% CI 4.0-5.4). With a median follow up of 28.6 months, the overall survival (OS) rates at 1 and 2 years were 47% and 15%, respectively. The 6-month PFS and 2-year OS rates were 11% and 10% in q3w cohort vs 36% and 29% in q1w cohort, respectively. In pts with disease control (n=26), median PFS and 2-year OS rate were 4.4 months and 11% in q3w cohort vs 9.1 months and 57% in q1w cohort, respectively. In a landmark analysis set at 2 months (1st restaging), median OS was longer in pts who had achieved disease control compared with those who had progressed (14.7 vs 6.8 months; p=0.03). By multivariate analyses, a PS of 0 (HR=0.38; p=0.02) and a baseline NLR ≤ 3 (HR=0.40; p=0.005) were associated with longer survival, while no associations were detected between OS and age, sex, histology, EORTC score and treatment-free interval on prior therapy. Median OS were 17.4 vs 8.0 months in pts with PS 0 or PS 1-2 and 15.7 vs 5.6 months in pts with NLR ≤ or > 3, respectively. Conclusions: Based on these results, NGR-hTNF 0.8 µg/m2 q1w is currently tested in a placebo-controlled phase II trial as a maintenance treatment in MPM pts who did not progress after 6 cycles of first-line chemotherapy and in a double-blind phase III trial evaluating best investigator’s choice ± NGR-hTNF in relapsed MPM.