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Poster Display session 1

5582 - Exploring Resistance to Nivolumab [NIV] applying an Immune Genomic Signature (IGS) in advanced pretreated NSCLC [PRINCiPe study]


28 Sep 2019


Poster Display session 1


Tumour Site

Non-Small Cell Lung Cancer


Sara Pilotto


Annals of Oncology (2019) 30 (suppl_5): v602-v660. 10.1093/annonc/mdz260


S. Pilotto1, E. Vita2, I. Sperduti3, V.P. Di Noia2, G. Grizzi1, E. D'Argento4, M. Simbolo5, C. Vicentini5, A. Caliò5, A. Mafficini5, L. Carbognin6, V. Corbo7, A. Gkountakos5, A. Santo1, M. Brunelli5, M. Martini5, A. Scarpa7, M. Milella1, G. Tortora8, E. Bria6

Author affiliations

  • 1 Department Of Oncology, University of Verona Hospital Trust, 37134 - Verona/IT
  • 2 Department Of Oncology, Università Cattolica del Sacro Cuore, Roma/IT
  • 3 Biostatistical Unit - Clinical Trials Center, Bio-Statistics Unit, Regina Elena National Cancer Institute, 00144 - Roma/IT
  • 4 Department Of Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma/IT
  • 5 Department Of Diagnostics And Public Health, Section Of Anatomical Pathology, University of Verona Hospital Trust, Verona/IT
  • 6 Division Of Gynecologic Oncology, Department Of Woman And Child Health, Fondazione Policlinico Universitario A. Gemelli, I.R.C.C.S., Università Cattolica del Sacro Cuore, 00168 - Roma/IT
  • 7 Department Of Diagnostics And Public Health And Arc-net Research Centre, Section Of Anatomical Pathology, University of Verona Hospital Trust, Verona/IT
  • 8 Department Of Medical Oncology, Azienda Ospedaliera Universitaria Integrata Verona, Verona/IT


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Abstract 5582


Specific genomic abnormalities in immune-escape/editing-related genes have been demonstrated to be associated with immunotherapy resistance. In the light of this hypothesis, with the final aim to identify a potential predictive signature for immunotherapy, we designed the PRINCiPe (Predictors of Resistance to Immunotherapy with NIV) study in advanced pretreated non-small cell lung cancer (APNSCLC).


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). Endpoints of the PRINCiPe study were overall-, progression-free-survival (OS/PFS) and objective response rate (ORR).


Overall, 44 APNSCLC pts were collected and analysed. Main patients characteristics: median age 69.5 yrs, median number of previous lines 3 (2-5), 2nd line NIV (75.0%), male/female 77.3/22.7%, squamous/non-squamous 31.8/68.2%, EGFR mutant 5 (11.4%), median follow-up 6.8 months (range 1-23), deaths 24 (54.5%). JAK3/JAK2 (7/3 pts, 15.9/6.8%) CNV and IFNAR2 SM (4 pts, 9.1%) were the most frequent (>1 pts) abnormalities. Those pts (n = 15) harboring JAK3, PIAS4, PTPN2, STAT3, IFNAR2 SM and/or JAK2/3 CNV (IGS+) had a significantly lower PFS than those without (IGS-) (median PFS 2.8 vs. 6.6 months; p = 0.006), while a trend towards significance was observed in terms of OS (median OS 5.1 vs. 13.0 months for IGS+ and IGS-, respectively; p = 0.06 log-rank, p = 0.05 Tarone-Ware). At multivariate analysis, IGS+ was independently associated with a shorter PFS (HR 2.64, 95% CI 1.3-5.4, p = 0.008). IGS+ pts were significantly more probable to be affected by liver metastases than those without (p = 0.01).


The identified IGS was able to select APNSCLC pts with a significant lower chance to benefit from NIV, supporting the existence of an intrinsic genomic-detectable resistance. Further analyses are ongoing, including a comprehensive transcriptome analysis.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Emilio Bria.


University of Verona.


S. Pilotto: Honoraria (self): AstraZeneca, BMS, Roche, MSD, Boeringher Ingelheim; Research grant / Funding (self): AIRC ; Travel / Accommodation / Expenses: BMS, Roche, AstraZeneca, Boeringher Ingelheim. M. Milella: Honoraria (self): Pfizer, EUSA Pharma, AstraZeneca. E. Bria: Honoraria (self): MSD, AstraZeneca, Celgene, Pfizer, Helsinn, Eli Lilly, BMS, Novartis, and Roche; Research grant / Funding (self): AIRC. All other authors have declared no conflicts of interest.

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