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Poster display session

5355 - Estimation of benefice to anti-PD-(L)1 for metastatic patients by real-time quantitative and functional estimation of immune infiltrate with RNAseq

Date

10 Sep 2017

Session

Poster display session

Topics

Cancers in Adolescents and Young Adults (AYA);  Immunotherapy;  Translational Research

Presenters

Loic Verlingue

Citation

Annals of Oncology (2017) 28 (suppl_5): v403-v427. 10.1093/annonc/mdx376

Authors

L. Verlingue1, L. Mahjoubi1, D. Brandao2, S. Michiels3, S. Champiat4, S. Aspeslagh5, Y. Loriot6, Y. El Dakdouki7, S. Postel-Vinay1, C. Nicotra1, H. Zouhri1, G. Chartier1, E. Solary8, O. Bernard9, D. Gautheret2, E. Angevin1, A. Hollebecque1, A. Marabelle1, F. André10, J. Soria1

Author affiliations

  • 1 Drug Development Department (ditep), Gustave Roussy, 94805 - Villejuif/FR
  • 2 Bioinformatic Platform, Gustave Roussy, 94200 - Villejuif/FR
  • 3 Biostatistics, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 4 Inserm U981, Gustave Roussy, 94805 - Villejuif/FR
  • 5 Drug Development Department (ditep), Gustave Roussy Cancer Campus, 94805 - Villejuif/FR
  • 6 Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 7 Duertec, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 8 Umr 1170, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 9 Umr, Gustave Roussy, 94805 - Villejuif/FR
  • 10 Breast Cancer Unit, Department Of Medical Oncology, Gustave Roussy Institut de Cancérologie, 94805 - Villejuif/FR
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Resources

Abstract 5355

Background

There is a current need to broadly evaluate the ability of RNA sequencing (RNAseq) to identify patients that will respond or not to PD-1 or PDL-1 immune checkpoint blockers (ICB) across metastatic tumor types.

Methods

RNA sequencing analysis were prospectively performed by a unique platform on patients’ fresh frozen biopsies collected in the MOSCATO (NCT01566019) and MATCH-R (NCT02517892) prospective trials, ongoing at Gustave Roussy. We have analyzed more than 100 signatures related to immune cell types or immune mechanisms with several methods, and have evaluated their relation to PFS and OS under ICB, up to January 2017.

Results

RNAseq performed on a frozen tumor biopsy before receiving an ICB were available for 67 patients. The median time between the biopsy and start of the ICB was 41 days. The results of RNAseq analysis were available within a median of 42 days. The majority of patients were affected by either head-and-neck carcinomas (N = 12), bladder carcinomas (N = 11) or lung adenocarcinomas (N = 11). The majority of patients were treated with PD-1 (N = 41) or PD-L1 (N = 28) inhibitors either in monotherapy or in combination. The immune infiltrate was heterogeneous across patients and neither related to the histology nor to the location of the biopsy. The top RNAseq pipeline of analysis related to PFS were GSVA enrichment method and the combination of GSEA on Z transformed log TPM pipeline. Taken individually, 60% of the tested signatures had a significant relation to PFS under ICB whatever the pipeline used (logrank FDR

Conclusions

The use of RNAseq to orient patients to ICB is feasible. Estimation of immune infiltrate and function from RNAseq may be associated with treatment benefice either in term of PFS or in term of OS.

Clinical trial identification

MOSCATO (NCT01566019) and MATCH-R (NCT02517892)

Legal entity responsible for the study

Jean Charles Soria

Funding

None

Disclosure

L. Verlingue: Consultant for Adaptherapy. J-C. Soria: Consultancy fees from AstraZeneca, Astex, Clovis, GSK, Gammamabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, Pharmamar Pierre Fabre, Roche-Genentech, Sanofi, Servier, Symphogen, Takeda. All other authors have declared no conflicts of interest.

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