Data from Association of Antifolate Response Signature Status and Clinical Activity of Pemetrexed-Platinum Chemotherapy in Non-Small Cell Lung Cancer - The Piedmont Study

Abstract Purpose: The Piedmont study is a prospectively designed retrospective evaluation of a new 48-gene antifolate response signature (AF-PRS) in patients with locally advanced/metastatic NS-NSCLC treated with pemetrexed-containing platinum doublet chemotherapy (PMX-PDC). The study tested the hypothesis that AF-PRS selects for patients with NS-NSCLC that preferentially respond to PMX-PDC, with a goal of providing clinical support for AF-PRS as potential diagnostic test. Experimental Design: Residual pre-treatment FFPE tumor samples and clinical data were analyzed from 105 patients treated with 1st-line (1L) PMX-PDC. 95 patients had sufficient RNA sequencing (RNAseq) data quality and clinical annotation for inclusion in the analysis. Associations between AF-PRS status and associate genes, and outcome measures including progression-free survival (PFS) and clinical response were evaluated. Results: Overall, 53% of patients were AF-PRS(+), which was associated with extended PFS, but not OS, vs. AF-PRS(-) (16.6 vs. 6.6 mo; p = 0.025). In patients who were Stage I-III patients at time of treatment, PFS was further extended in AF-PRS(+) vs. AF-PRS(-) (36.2 vs. 9.3 mo; p = 0.03). Complete response (CR) to therapy was noted in 14 of 95 patients. AF-PRS(+) preferentially selected a majority (79%) of CRs, which were evenly split between patients Stage I-III (6 of 7) and Stage IV (5 of 7) at time of treatment. Conclusions: AF-PRS identified a significant population of patients with extended PFS and/or clinical response following PMX-PDC treatment. AF-PRS may be a useful diagnostic test for patients indicated for systemic chemotherapy, especially when determining the optimal PDC regimen for locally advanced disease.