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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

4511 - Gene expression (GE)-based biomarkers associated with nivolumab response in a real-life cohort of patients with metastatic non-small cell lung cancer (mNSCLC)

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Nina Radosevic-Robin

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

N. Radosevic-Robin1, S. Ong2, S.E. Warren3, M. Kossai1, C. Godfraind4, M. Masson5, H. Janicot6, P. Merle6, P. Dubray-Longueras5, X. Durando5, P. Morel7, A. Cesano8, F. Penault-Llorca1

Author affiliations

  • 1 Pathology, Centre Jean Perrin, 63011 - Clermont-Ferrand/FR
  • 2 Bioinformatics, NanoString Technologies, Inc., Seattle/US
  • 3 Biology, NanoString Technologies, Inc., WA 98109 - Seattle/US
  • 4 Pathology, University Hospital Center of Clermont-Ferrand, Clermont-Ferrand/FR
  • 5 Medical Oncology, Centre Jean Perrin, 63011 - Clermont-Ferrand/FR
  • 6 Pneumology, University Hospital Center of Clermont-Ferrand, Clermont-Ferrand/FR
  • 7 Medical Affairs, NanoString Technologies, Inc., WA 98109 - Seattle/US
  • 8 Medical Affairs, NanoString Technologies, Inc., Seattle/US
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Resources

Abstract 4511

Background

Robust and versatile biomarkers are urgently needed to identify cancer pts who are likely to benefit from immune checkpoint inhibitors (ICI). The Tumor Inflammation Signature (TIS) is an 18-gene signature measuring the suppressed adaptive immune response necessary for pts clinical benefit from ICI (Ayers, J Clin Invest 2017). This retrospective study evaluated the performance of TIS and additional GE signatures assessing pathways associated with immune evasion in mNSCLC pts, treated with nivolumab as per label (2nd+ line), in two French cancer centers.

Methods

RNA from primary FFPE tumor samples from 77 immunotherapy-naïve mNSCLC pts, treated with nivolumab monotherapy, was profiled with a β-version of the NanoString® IO 360 GE panel, which includes the TIS and other tumor and immune biology signatures. The statistical analysis treated associations of GE and clinical response.

Results

In the whole cohort analysis, samples from pts who experienced clinical benefit showed an “inflamed” phenotype. Specifically, TIS was significantly higher in the responder group compared to non-responders (p = 0.005, non-adjusted). A similar association was observed for myeloid and macrophage scores (p = 0.001 and p = 0.002, respectively) as well as for PDCD1 (PD1), CD274 (PDL1), and CTLA4 (p = 0.05, 0.001, 0.02, resp.). In a subtype analysis, squamous carcinomas showed a less inflamed phenotype than adenocarcinomas but had elevated proliferation, glycolysis and hypoxia scores, as well as increased ARG1 and NOS2. In contrast, in the independent subtype analysis, both TIS and additional immune signatures remained associated with clinical response.

Conclusions

TIS and other immune signatures predicted response to nivolumab single agent in a real-life cohort of pts, in both adeno- and squamous mNSCLC. Thus, assessing GE patterns can give insight into different mechanisms of immune evasion operating at the single patient level. Additional analyses of this cohort, evaluating the NanoString® IO 360 signatures and single gene expressions, with regard to various other clinical and molecular tumor features, will be presented.

Clinical trial identification

Legal entity responsible for the study

NanoString Technologies, Inc.

Funding

NanoString Technologies, Inc.

Editorial Acknowledgement

Disclosure

S. Ong, S.E. Warren, P. Morel, A. Cesano: Employee and stockholder: NanoString. All other authors have declared no conflicts of interest.

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