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B. Hunis



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    OA10 - EGFR Mutations (ID 382)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Biology/Pathology
    • Presentations: 1
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      OA10.07 - Report on Liquid Biopsies from Advanced Lung Adenocarcinoma Patients and Correlation with Their Tumor Biopsy Profiles (ID 4826)

      11:00 - 12:30  |  Author(s): B. Hunis

      • Abstract
      • Presentation
      • Slides

      Background:
      Liquid biopsy (LBx) has emerged as an alternative tool for the management of advanced lung cancer patients (pts) identifying driver mutations, and hence, improving personalized medicine. There are still controversial issues such as standardization, validation of different technologies, concordance with tissue molecular profile results (TMPR), and others. LBx offers many advantages including non-invasive, bypass tumor heterogeneity, an opportunity for serial measurements to evaluate response or early recurrence, and others.

      Methods:
      Guardant 360 was analyzed in 100 consecutive stage IV or recurrent lung adenocarcinoma (adeno) pts. Guardant 360 is a panel of 70 genes including single nucleotide variations, amplifications, translocations, and short insertions/duplications/deletions in exons 19 and 20 of the EGFR, and others. Cell-free DNA (cfDNA) is extracted from plasma and genomic alterations are analyzed by massively parallel sequencing of amplified target genes. TMPRs from each subject was obtained or recovered for comparison with their LBx counterparts. TMPRs from this cohort was developed in different CLIA laboratories

      Results:
      69 pts were females; median age 72 (range, 27-99). 84/100 pts had at least 1 genomic alteration by LBx (range, 1-10). Most common abnormalities found in LBx were: TP53 (37 pts), EGFR (35 pts), NF1 (20 pts), KRAS (12 pts), MET (14 pts). From this 84 pts with + LBx results, 67 pts (80%) had TMPRs for comparison. Main reason for lack of TMPRs: insufficient tumor (19/100; 19%). For comparison between the 2 modalities, we considered all pts with available results in both tests; hence, 81 pts were used to compare tumor biopsy (TBx) vs. LBx. 37 pts out of 81 (46%) had at least 1 similar genomic abnormality found in both TBx and LBx, respectively. Most of the concordance was in EGFR alterations (19/28; 68%). LBx caught 16 additional EGFR genomic aberrations not being identified by TBx. A total of 35 EGFR genomics aberrations were identified in LBx; 16/35 EGFR mutations found in LBx were actionable and 5 of these 16 actionable EGFR mutant cases were only found in LBx not in TBx.

      Conclusion:
      LBx offers an alternative to identify genomic alterations. Still, insufficient tumor is the major reason for lacking of TMPRs. EGFR mutations are the most common actionable mutations found in LBx; also, it has a high correlation with TBx (68%). LBx identified more gene abnormalities than TBx, and in some cases, the actionable EGFR mutations were found only in LBx sample.

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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
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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 - 15:45  |  Author(s): B. Hunis

      • 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.