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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

3259 - Preliminary results of PRINCiPe (Predictors of Resistance to Immunotherapy with Nivolumab [NIV]) study in advanced pretreated non-small-cell lung cancer (APNSCLC), investigating the role of an Immune Genomic Signature (IGS) including JAK2, JAK3, PIAS4, PTPN2, STAT3, IFNAR2 alterations.

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

Topics

Tumour Immunology;  Translational Research

Tumour Site

Presenters

Sara Pilotto

Citation

Annals of Oncology (2018) 29 (suppl_8): viii493-viii547. 10.1093/annonc/mdy292

Authors

S. Pilotto1, G. Grizzi1, I. Sperduti2, M. Simbolo3, C. Vicentini3, A. Caliò3, M. Caccese1, A. Mafficini3, L. Carbognin1, V. Corbo3, A. Gkountakos3, A. Santo1, M. Infante4, M. Brunelli3, A. Scarpa5, G. Tortora1, E. Bria6

Author affiliations

  • 1 Medical Oncology, University of Verona, AOUI Verona, 37134 - Verona/IT
  • 2 Biostatistics, Regina Elena National Cancer Institute, Rome/IT
  • 3 Department Of Diagnostics And Public Health, Section Of Anatomical Pathology, University and Hospital Trust of Verona, Verona/IT
  • 4 Thoracic Surgery, AOUI Verona, 37134 - Verona/IT
  • 5 Arc-net Research Centre And Department Of Diagnostics And Public Health - Sectio, AOU Integrata Verona "Borgo Roma", 37134 - Verona/IT
  • 6 Uoc Oncologia Medica, Università Cattolica del Sacro Cuore - Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 - Rome/IT

Resources

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Abstract 3259

Background

Although immunotherapy impressively improved the outcome of APNSCLC, many patients (pts) rapidly progress. The mechanism of resistance may be influenced by genomic abnormalities in immune-escape/editing genes.

Methods

FFPE-tumor blocks of APNSCLC pts undergone NIV were retrospectively sequenced for Somatic Mutations/Copy Number Variations (SM/CNV) (Ampliseq 17-genes customized panel: APLNR, B2M, IFNAR1, IFNAR2, IFNGR1, IFNGR2, IRF9, JAK1, JAK2, JAK3, PIAS4, PTPN2, SOCS1, STAT1, STAT2, STAT3, TYK2). End-points of PRINCiPe study: overall-, progression-free-survival (OS/PFS) and objective response rate (ORR).

Results

24 APNSCLC pts were gathered (median age 69.5 yrs, median number of previous lines 3 [2-5], 2nd line NIV [70.8%], male/female 79.2/20.8%, squamous/non- squamous 41.7/58.3%, EGFR mutant 5 [20.8%], median follow-up 6.8 months [range 1-23], deaths 14 [58.3%]). JAK3/JAK2 (6/3 pts, 25/12.5%) CNV, and IFNAR2/STAT3 SM (2 pts, 8.3%) were the most frequent abnormalities. Pts (12) with JAK3, PIAS4, PTPN2, STAT3, IFNAR2 SM and/or JAK2/3 CNV (IGS+) had a significantly lower OS/PFS than those without (IGS-). At multivariate analysis, IGS+ was independently associated with shorter OS (HR 4.90, 95% CI 1.40-16.5, p = 0.01) and PFS (HR 6.10, 95% CI 2.0-18.7, p = 0.001); the (previous) surgery was significantly associated with longer PFS (HR 4.20, 95% CI 1.1-11.4, p = 0.03). IGS+ pts were significantly more associated with the presence of liver metastases (p = 0.04). A trend towards lower activity of NIV in EGFR+ pts was found.Table: 1417P

IGS+IGS-p-value
ORR (%, 95% CI)-16.6% (2-31)0.09
Median OS (months, 95% CI)4 (1-8)13 (n.e.)0.046
Median PFS (months, 95% CI)3 (2-3.5)6 (5-9)0.002

Conclusions

The derived IGS appears to identify APNSCLC pts with a lower chance to benefit from NIV, supporting intrinsic resistance. Given the small sample, a prospective larger and external validation is ongoing.

Clinical trial identification

Legal entity responsible for the study

Emilio Bria.

Funding

University of Verona.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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Presenter: Qi Ling

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

Resources:

Abstract

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