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  P2.09 - Pathology (ID 174)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 31202

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    P2.09-03 - Prognostic Value of Mutated KRAS in Circulating Tumor DNA Prior to Therapy in Patients with Lung Adenocarcinoma (ID 1901)

    10:15 - 18:15  |  Author(s): Hong Yan Dai
    • Abstract
    • Slides

    Background
    

    Studies show an association between total tumor load and the amount of circulating cell-free tumor DNA (ctDNA) in blood, and that detectable ctDNA is a negative prognostic factor. KRAS mutations (mutKRAS) are the most common oncogenic drivers in lung adenocarcinomas (lungAC) and are found in 25-30 % of the patients. We hypothesized that the concentration of mutKRAS in plasma ctDNA is associated with outcomes in patients with lungAC harboring KRAS mutations, and aimed to investigate whether there was an association with disease stage, progression free (PFS) and overall survival (OS).

    Method
    

    Blood samples collected prior to first treatment from 61 lungAC-patients with known mutKRAS in tumor DNA were analyzed. Digital droplet PCR was used for detection and quantification of mutKRAS in the plasma samples. The false positive rate for each mutKRAS assay was determined using cfDNA from healthy donors. A sample was defined as "positive" if the mutKRAS level was above the false positive rate. Mann-Whitney U test was used to compare PFS and OS between those with not-detectable and those with detectable mutKRAS ctDNA. Log-rank and Cox proportional hazard methods were used for survival analyses. One-way ANOVA was used to compare the concentration of mutKRAS between disease stages.

    Result
    

    Median age was 68 years (range 47-83), all patients were former/current smokers, 39.3% were men; 39.3% had stage I, 18.0% stage II, 24.6% stage III and 18.0% stage IV; 55.7% had performance status (PS) 0, 39.3% PS 1, and 4.9% PS 2; 70.5% underwent surgery, 4.9% curative radiochemotherapy and 24.6% palliative treatment. Overall, 26.2% had detectable mutKRAS in ctDNA with a median of 119.68 (range:16.66-1208) copies/ml plasma.The proportion of patients with mutKRAS in plasma ctDNA increased with higher disease stage (stage I: 0%, II: 18%, III: 47%, and IV: 64 %; p=0.006). Patients with plasma mutKRAS had significantly shorter PFS ( 11.9 vs. 23.5 months; p=0.012) and OS ( 15.8 vs. 23.5 months; p=.0.010) than those without. The mutKRAS ctDNA concentration was significantly associated with both shorter PFS (HR 1.009, 95% CI 1.004-1.013; p<0.001) and OS (HR 1.007, 95% CI 1.003-1.011; p=0.001).The associations remained statistically significant in the multivariate analyses adjusting for baseline characteristics (gender, age, disease-stage, PS, treatment) for both PFS (HR 1.009, 95% CI 1.003-1.014; p=0.002) and OS (HR 1.008, 95% CI 1.002-1.015; p=0.008).

    Conclusion
    

    The concentration of plasma mutKRAS increased with higher disease stage. Patients with detectable plasma mutKRAS had worse PFS and OS than patients without. The concentration of mutated KRAS was independently associated with worse PFS and OS.

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