The efficacy of maintenance chemotherapy (CT) in advanced NSCLC is still under investigation. The multicenter, open label, randomized, phase II MA.NI.LA trial aimed to assess the activity of metronomic oral vinorelbine versus close observation as maintenance treatment following platinum-based CT in patients with advanced NSCLC. Serum angiogenesis biomarkers and the plasma microRNA signature classifier (MSC) associated with tumor aggressiveness in NSCLC patients were here investigated as prognostic and predictive factors.
119 advanced NSCLC patients with stable disease after platinum-based CT received maintenance metronomic oral vinorelbine (ARM A) or close observation (ARM B). The primary endpoint of the trial was progression free survival (PFS). Plasma samples for biomarkers evaluation were collected at the baseline from all patients. Concentrations of VEGFA and THBS1 were determined using EIA kit (Chemicon International). To determine MSC risk level, custom made microfluidic cards (Thermo Fisher) were adopted to analyze 8 samples simultaneously by RT-qPCR. Cox regression model was used to evaluate the association of biomarkers to PFS and OS.
In the whole cohort, median age was 68.8; M/F: 79/40; stage IIIb/IV:14/105; adeno/other:73/46; PS 0-1/2:113/7. In front of a median follow up of 23.9 months, median PFS was 4.3 and 2.8 months for ARM A and ARM B, respectively (HR = 0.73; 90%CI 0.53-0.999; p = 0.0493). Considering all 119 patients, high VEGFA and THBS1 plasma levels and positive MSC expression were associated with shorter both PFS and OS. HR for 1000 unit, VEGF: 1.56 (90%CI 0.99-2.46; p = 0.054); HR for 10000 unit, THBS1: 1.16 (90%CI 0.97-1.38; p = 0.114); HR for MSC pos vs neg: 1.61 (90%CI 1.05-2.47; p = 0.028). Similar results were obtained considering OS. No interaction between treatment effect and biomarker values were detected.
In advanced NSCLC following platinum-based induction CT, metronomic oral vinorelbine showed a modest, but significant improvement in PFS. In addition, VEGF and MSC could be considered as prognostic but not predictive factors
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