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J. Wang



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    MINI 25 - Trials, Radiation and Other (ID 142)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      MINI25.04 - Utilizing Molecular Profiling to Identify Potential Therapies in Sarcomatoid Lung Cancer (ID 655)

      17:00 - 17:05  |  Author(s): J. Wang

      • Abstract
      • Presentation
      • Slides

      Background:
      Sarcomatoid lung cancer (SLC) is an aggressive subset of poorly differentiated non-small cell lung carcinoma (NSCLC), comprising just one percent of all NSCLC. Further elucidation of this unique histological entity has been hampered by a lack of large-scale clinical trial evidence. The National Comprehensive Cancer Network (NCCN) contains no clear direction regarding optimal management. The purpose of this study, therefore, is to identify potential therapeutic options for this disease using a multiplatform, biomarker-directed approach.

      Methods:
      In total, 48 SLC specimens analyzed via a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ) consisting of gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]) and gene amplification (CISH or FISH) were retrospectively evaluated.

      Results:
      High rates of PD-L1 (83.3%, 5/6) and PD-1 (80.0%, 4/5) protein expression by IHC imply benefit to recently-approved compounds. EGFR amplification by ISH (18.8%, 3/16) and MET amplification (9.5%, 2/21) were independent of EGFR mutation in this group. No ALK, HER2 or ROS1 ISH abnormalities were detected. Mutational analysis shows the highest mutation rates in TP53 (50.0%, 7/14), KRAS (44.4%, 16/36), cKIT (5.3%, 1/19), EGFR (5.1%, 2/39) and BRAF (4.8%, 1/21). The two EGFR mutations detected were L858R and exon 20 insertion.

      Conclusion:
      Multiplatform profiling identified multiple potential actionable targets with various approved therapies. PD-1 and PD-L1 overexpression rate was comparable to that published in sarcomatoid renal cell carcinoma. Therefore, new immunotherapies should be prospectively tested in sarcomatoid disease specific trials based on high PD-1/PD-L1 overexpression. Our finding of low EGFR mutational frequency is consistent with previous, published findings in this disease. Lower rates of ALK, ROS1, and EGFR are not surprising given SLC’s association with smoking. Clinical trials evaluating the benefit of imatinib and vemurafenib in subgroups with cKIT or BRAF mutations may be worthwhile.

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