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- W2890461353 abstract "9078 Background: Patient selection for PD-1 inhibitors in NSCLC is still based on imperfect screening biomarkers, including PD-L1 tumor expression and tumor mutational burden. We hypothesized that pretreatment molecular profile of ctDNA and its early kinetics during treatment could represent a reliable and non-invasive approach to determine response. Methods: Up to 4 serial plasma samples were prospectively collected from patients with advanced NSCLC treated with nivolumab as second line therapy: i) pretreatment, ii) at 1 month, iii) at the first CT-scan, iv) at progression. Plasma NGS was performed using InVisionSeq, tagged amplicon sequencing of hotspots and coding regions from 36 genes. The early kinetics (1 month) of ctDNA through treatment was analyzed along with specific baseline alterations as early indicators of response to immunotherapy. Results: 80 specimens from 33 patients underwent NGS. Alterations in ctDNA were detectable in 25/33 baseline samples. The most frequently detected alterations at baseline were TP53 (54.4%); KRAS (33.3%); STK11 (24.2%); and NFE2L2 (9%). Lack of detectable ctDNA at baseline in 6/8 patients correlated with progressive disease (PD). Studying 23 patients for whom serial specimens were available with ctDNA detected at baseline, plasma response (kinetics of ctDNA between baseline and 1 month specimens) was correlated with clinical outcomes (RECIST) in 18/23 cases (11/13 with overall response (OR) or stable disease (SD) and 7/10 with PD). Furthermore, ctDNA demonstrated potential predictive ability on outcomes by analyzing specific alterations and type of nucleotide change (transversion vs transition). Transversions in KRAS and TP53 were detected in 13/14 baseline cases demonstrating clinical benefit (OR+SD) while 8/11cases from patients who went on to have PD were enriched with transitions or STK11 co-mutations with TP53 or KRAS transversions. Conclusions: Plasma cell-free DNA analysis using NGS could be an additional screening assay to identify patients likely to derive benefit from anti-PD-1 therapy, particularly when tissue is unavailable." @default.
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- W2890461353 date "2018-05-20" @default.
- W2890461353 modified "2023-09-30" @default.
- W2890461353 title "Early prediction of outcomes to PD1 inhibitors in non-small cell lung cancer (NSCLC) using next generation sequencing (NGS) of plasma circulating tumor DNA (ctDNA)." @default.
- W2890461353 doi "https://doi.org/10.1200/jco.2018.36.15_suppl.9078" @default.
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