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Edward S Kim



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    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-62 - Circulating Tumor DNA Assay and Survival in Patients with Metastatic, Non-Small Cell Lung Cancer (ID 935)

      10:15 - 18:15  |  Author(s): Edward S Kim

      • Abstract

      Background

      Circulating tumor DNA (ctDNA) sampling has emerged as a non-invasive approach to characterizing genomic alterations in blood of patients (pts) with metastatic, non-small cell lung cancer (mNSCLC). ctDNA or ‘liquid biopsy’ may be used to guide treatment and prognosis.

      Method

      This was a prospective pilot study of pts with histologically confirmed mNSCLC. Pts were enrolled prior to initiating a new line of therapy. Tumor and ctDNA specimens were collected prior to treatment and radiology scans were performed at standard intervals; ctDNA collections continued until progression. ctDNA was assessed by Inivata (InvisionFirst) using amplicon-based targeted next generation sequencing with 36-gene panel to detect single nucleotide variants, short insertions/deletions, copy number variations and structural variants.

      ctDNA features were calculated for each pt and included number of genomic alterations (numGA), number of mutations (numMUT), number of amplifications/fusions (numAMPFUS), sum mutant allele frequency (sumMAF), and maximum mutant allele frequency (maxMAF).

      Univariate and multivariable Cox proportional hazards models were used to identify ctDNA features associated with progression-free survival (PFS). ctDNA from baseline (T0) to the blood collection closest to progression or censor date (T1) was used to assess change in sumMAF and maxMAF. All models included ctDNA features as continuous variables.

      Result

      27 pts were evaluable. 85.19% were white; 37.04% were male. 85.19% were adenocarcinoma histology; remaining were squamous. 45.83% received prior systemic therapy. Average number of lines of prior therapy was 1.81. 44.44% had prior radiation therapy. 81.48% of pts had at least one genomic alteration detected in ctDNA at baseline. The median numGA, numMUT, and numAMPFUS, maxMAF, sumMAF was 2.00, 2.00, 0.00, 1.61, and 2.34 respectively. TP53, KRAS, and EGFR were the most frequently identified genomic alterations (59.26%, 25.93%, and 22.22%, respectively). EGFR alterations were the most commonly identified genomic alteration in ctDNA. 86.00% of EGFR alterations were actionable. Univariate Cox regression analysis identified numAMPFUS (HR=3.12, p=0.01), sumMAF (HR=1.02, p=0.02), and maxMAF (HR=1.05, p=0.00) to be significantly associated with PFS. Only maxMAF was retained in the final multivariable Cox model. Each percentage point increase in maxMAF from T0 to T1 resulted in a 4% decrease in the risk of progression/death (HR=0.96, p=0.08).

      Conclusion

      In this pilot study, pts with higher levels of baseline maxMAF detected in ctDNA were associated with increased risk of progression/death. Following initiation of treatment, results suggest increased change in maxMAF may be associated with a decreased risk of progression/death.