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D. Rangachari



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    MA 06 - Lung Cancer Biology I (ID 660)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Biology/Pathology
    • Presentations: 1
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      MA 06.02 - Cytology and Surgical Pathology Specimens are Comparable Testing Substrates for PD-L1 Immunohistochemistry in Lung Cancer (ID 9063)

      15:45 - 17:30  |  Author(s): D. Rangachari

      • Abstract
      • Presentation
      • Slides

      Background:
      Immunohistochemical (IHC) testing for programmed death ligand 1 (PD-L1) expression by non-small cell lung cancer (NSCLC) specimens has become standard of care to help select immune checkpoint inhibitor therapy. The companion IHC assay for pembrolizumab has been validated and approved for use on surgical pathology specimens; however, the performance of this assay when applied to cytology specimens is not well characterized.

      Method:
      Following IRB approval, all NSCLC cytology or surgical pathology specimens obtained from 11/2015 to 5/2017 at our institution that were tested for PD-L1 expression by a commercial vendor (Integrated Oncology/LabCorp, NY) using the FDA-approved companion diagnostic PD-L1 clone 22C3 pharmDx kit on the Dako Automated Link 48 platform (Dako, Carpenteria, CA) were identified. Patient cohorts where testing was performed on diagnostic cytology vs. surgical pathology specimens were compared. Tumor PD-L1 expression was stratified by clinically relevant groups: <1%, 1-49%, and ≥50%. Tumor genotyping results for EGFR, KRAS, ALK, and ROS1 were also collected.

      Result:
      Cytology formalin-fixed paraffin-embedded (FFPE) cell blocks included endobronchial ultrasound transbronchial needle aspirates (57%), pleural/pericardial fluids (28%), fine needle aspirates (13%), and bronchial washings/lavages (2%). Surgical FFPE specimens included small core/incisional biopsies (60%), bronchial biopsies (12%), and large resections (28%). PD-L1 testing was successful for over 96% (223/232) of specimens (Table). Overall, EGFR mutations were more frequent with no/low PD-L1 expression, ALK rearrangements with high PD-L1 expression, but no relationship between KRAS mutations and PD-L1 expression.

      PD-L1 Tumor Proportion Score Stratified by Specimen Type
      Cytology Cell Block Surgical Pathology
      <1% PD-L1 TPS 35 (37.2%) 52 (37.7%)
      1-49% PD-L1 TPS 20 (21.3%) 35 (25.4%)
      ≥50% PD-L1 TPS 33 (35.1%) 48 (34.8%)
      Failed Analysis 6 (6.4%) 3 (2.2%)
      Total 94 (100%) 138 (100%)
      Chi-squared value=2.95, p>0.39 (not significant); TPS=tumor proportion score

      Conclusion:
      For NSCLC, no statistically significant differences in PD-L1 expression patterns were observed between cytology cell block and surgical pathology specimens, implying that in clinical practice any adequate cytology cell block or surgical pathology specimen could be utilized for testing. Importantly, analysis of clinical outcomes with use of first line pembrolizumab based on cytology vs surgical pathology specimen PD-L1 ≥50% expression is currently ongoing.

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    P3.03 - Chemotherapy/Targeted Therapy (ID 719)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
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      P3.03-025 - Tumor Biomarkers for the Routine Care of Advanced Non-Small-Cell Lung Cancer: A Decade of Experience in Implementing Predictive Genomic Events (ID 10193)

      09:30 - 16:00  |  Author(s): D. Rangachari

      • Abstract
      • Slides

      Background:
      Although a growing list of mandatory genomic/immune-based biomarkers are now routinely integrated into the management of advanced non-small-cell lung cancer (NSCLC), few reports have detailed the evolution of NSCLC predictive biomarker assessment in routine clinical practice.

      Method:
      We retrospectively probed 1,000+ NSCLC-patient pairs analyzed for predictive biomarkers from 2004 to 2017 at our institution and evaluated patterns of testing as well as correlation with clinical-pathologic characteristics.

      Result:
      The majority of 1,009 patient-tumor pairs had advanced adenocarcinoma with most specimens obtained from lung, mediastinal/hilar nodes, and pleura and with a similar distribution between surgical, small biopsy, and cytology specimens. All were tested for EGFR mutations, 895 for ALK rearrangement, 841 for KRAS mutation, 537 for ROS1 rearrangement, and 179 using comprehensive genomic profiling. Implementation of near-universal genomic biomarker testing for EGFR, ALK, ROS1 and PD-L1 occurred within the first year following evidence of activity/approval of a paired therapy. The failure rate after use of the best specimen for the most common tests was ≤5.5%. A quarter of tumors had a driver oncogene (EGFR/ALK/ROS1/BRAF-V600E) with an approved oral therapy, with the highest prevalence in patients with ≤15 pack-years tobacco use.

      Conclusion:
      Tumor biomarker testing in routine clinical NSCLC specimens at our institution evolves rapidly following approval of new therapies linked to diagnostic assays. Our practice’s decade-plus experience indicates that it will be feasible for the thoracic oncology community to continue to expand the use of predictive genomic and immune biomarkers using currently available clinical specimens.

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