Author of

• 17629

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  P2.03b - Poster Session with Presenters Present (ID 465)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 17668

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    P2.03b-039 - Cell-Free (cf) DNA and cfRNA levels in Plasma of Lung Cancer Patients Indicate Disease Status and Predict Progression (ID 4563)

    14:30 - 14:30  |  Author(s): J. Usher
    • Abstract

    Background:
    Cell-free circulating tumor DNA (ctDNA) and RNA (ctRNA) can be extracted from plasma of cancer patients (pts). Measuring dynamic changes in gene expression, allele-fractions of mutations and levels of nucleic acids per ml of plasma in metastatic patients has shown great potential for monitoring disease state and predicting outcome to antitumoral therapy in advance of imaging.
    
    Methods:
    We designed a clinical trial to measure gene levels of plasma ctDNA and ctRNA in metastatic pts with NSCLC, breast, and GI malignancies under treatment and correlate the levels with CT scans done assessing response for one-year clinical trial. CtDNA/ctRNA were extracted from plasma separated from patient whole-blood draws shipped at ambient temperature. CtRNA was reverse transcribed with random primers to cDNA. Levels of ctDNA/ctRNA were determined by real-time qPCR. Results of ctDNA/ctRNA tests were compared with responses (CR, PR, SD or PD) as determined by the CT scans. Levels of PD-L1 expression relative to β–actin were determined by qPCR.
    
    Results:
    We have enrolled 39 pts and we are presenting data from 15 pts with NSCLC. The first-line treatments were Carboplatin (40%, 6/15), Opdivo (26.7%, 4/15), Afatinib (13.3%, 2/15), Ceritinib (6.7%, 1/15), Crizotinib (6.7%, 1/15), and Taxotere/Cyramza (6.7%, 1/15). Histological subtypes were 73.3% (11/15) adeno, 20% (3/15) squamous, and 6.7% (1/15) other. The majority of patients were Caucasian (66.7%, 10/15), Hispanic (26.7%, 4/15), and African American (6.7%, 1/15). Levels of ctDNA and ctRNA were significantly correlated with one another across patient blood draws (r = 0.5781, p < 0.0001). After the first 2 cycles of therapy, 9 of the 15 patients achieved SD, of whom 8 were analyzed for ctDNA/ctRNA levels. In 7/8 of pts who had SD indicated by CT scan, CtDNA/ctRNA levels were stable, while the 2 PD pts showed significant increases in levels of ctDNA/ctRNA 4.8 weeks prior to progression. In the 2 SD pts treated with Opdivo, PD-L1 expression was stable during the cycles when CT scans also indicated an SD status.
    
    Conclusion:
    In almost 90% of the pts, constant ctDNA/ctRNA levels correlated with stable disease status as seen by CT; moreover, in 2 pts changes in the levels of both ct nucleic acids predicted progression about 5 weeks before CT scans. Importantly, the concordance between cDNA and cfRNA suggest that cfRNA can just as effective as cfDNA as a prognostic tool, while adding the extra dimension of gene expression.