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J.L. Aldrich



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    MA11 - Novel Approaches in SCLC and Neuroendocrine Tumors (ID 391)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      MA11.10 - Prospective Study of Genome-Wide Strexome and Transcriptome Profiling in Patients with Small Cell Lung Cancer Progressing after 1st Line Therapy (ID 4197)

      15:26 - 15:32  |  Author(s): J.L. Aldrich

      • Abstract
      • Presentation
      • Slides

      Background:
      Small cell lung cancer (SCLC) that has progressed after 1[st] line therapy has few effective treatments and no new class of approved therapies in over 20 years. Paired tumor-normal exome and transcriptome sequencing efficiency, coverage, cost, and analytics has improved over the last decade and has begun to be applied in the clinic. In this prospective study, we used genome-wide strexome (exome+structural variation) plus whole transcriptome sequencing (NGS) to identify genomic events and associated expression changes in advanced SCLC and attempt to prescribe systemic therapy based on the results (NCT02297087, study was funded by SU2C).

      Methods:
      After informed consent a prospective fresh frozen tumor biopsy was obtained. Germline DNA was extracted from PBMC and reference normal tissue RNA was obtained commercially. Strexome and RNA-seq libraries were prepped and NGS, data analysis, and reporting were performed in a CLIA-certified CAP accredited environment.

      Results:
      The study completed its accrual goal of 12 evaluable patients. There was one screen failure due to anticipated inadequate sample yield because of tumor location. The cohort included 10 women, median age was 56.5 years and had 3 never smokers. All patients received prior platinum-based chemotherapy and were receiving >1[st] line systemic treatment while awaiting NGS results. The minimum tumor content for successful NGS was 20%. The median turnaround time from sample collection to report was 27 days (range 21-38). Average strexome coverage was 420X (tumor), 200X (germline), with an average of 277 million RNA reads generated for tumors. All patients had ³2 clinically actionable targets identified (associated with a commercially available, FDA-approved drug by predefined rules), median 4 targets (range 2-8). Three patients received treatment identified by NGS. One has continuing partial response by RECIST 1.1 >8 months on a clinical trial involving PD-1 inhibitor+irinotecan (MLH1 mutation); treatment linked to NGS was already initiated prior to the report becoming available. One is too early to evaluate on olaparib (PARP1 mutation), and one had disease progression on dasatinib (KIT overexpression) as best overall response. One patient has not yet received NGS recommended therapy, and the remaining 8 evaluable patients had clinical deterioration or died before NGS recommended therapy was initiated.

      Conclusion:
      SCLC after 1[st] line therapy tends to have more rapid progression and deterioration making NGS application for systemic therapy challenging. Either applying NGS earlier in the earlier stages of disease course or further improvements in turnaround time may better address these challenges.

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