American Association for Cancer Research
ccr-22-2558_supplementary_table_s2_suppts2.xlsx (31.91 MB)

Supplementary Table S2 from Association of Antifolate Response Signature Status and Clinical Activity of Pemetrexed-Platinum Chemotherapy in Non–Small Cell Lung Cancer: The Piedmont Study

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posted on 2023-08-15, 08:22 authored by Joel R. Eisner, Gregory M. Mayhew, James M. Davison, Kirk D. Beebe, Yoichiro Shibata, Yuelong Guo, Carol Farhangfar, Farhang Farhangfar, Joshua M. Uronis, Jeffrey M. Conroy, Michael V. Milburn, David Neil Hayes, Kathryn F. Mileham

Expression Matrix of Patient Tumor Sample RNAseq





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 nonsquamous (NS) non–small cell lung cancer (NSCLC) treated with pemetrexed-containing platinum doublet chemotherapy (PMX-PDC). The study tested the hypothesis that AF-PRS identifies patients with NS-NSCLC who have a higher likelihood of responding positively to PMX-PDC. The goal was to gather clinical evidence supporting AF-PRS as a potential diagnostic test. Residual pretreatment FFPE tumor samples and clinical data were analyzed from 105 patients treated with first-line (1L) PMX-PDC. Ninety-five patients had sufficient RNA sequencing (RNA-seq) 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. Overall, 53% of patients were AF-PRS(+), which was associated with extended PFS, but not overall survival, versus AF-PRS(−) (16.6 months vs. 6.6 months; P = 0.025). In patients who were stage I to III patients at the time of treatment, PFS was further extended in AF-PRS(+) versus AF-PRS(−) (36.2 months vs. 9.3 months; 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 to III (six of seven) and stage IV (five of seven) at the time of treatment. 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.

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