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Proffered Paper - GU, non prostate 2

700O - Kidney ccRCC immune classification (KIC) enhances the predictive value of T effector (Teff) and angiogenesis (Angio) signatures in response to nivolumab (N)

Date

21 Sep 2020

Session

Proffered Paper - GU, non prostate 2

Presenters

Maxime Meylan

Citation

Annals of Oncology (2020) 31 (suppl_4): S550-S550. 10.1016/annonc/annonc274

Authors

M. Meylan1, B. Beuselinck2, C. Dalban3, Y. Vano4, N. Rioux Leclercq5, C. Sautès-Fridman1, E. Roussel6, A. Verbiest2, N. Chaput7, S. Terry8, C. Chevreau9, M. Gross Goupil10, A. Fléchon11, B. Laguerre12, S. CHABAUD13, F. Tantot14, D. Lambrechts15, B. Escudier16, W. Fridman1, L. Albiges17

Author affiliations

  • 1 Inflammation, Complement And Cancer, Centre de Recherche des Cordeliers, 75006 - Paris/FR
  • 2 Department Of General Medical Oncology, University Hospitals Leuven, 3000 - Leuven/BE
  • 3 Clinical Research Department, Centre Léon Bérard, 69008 - Lyon/FR
  • 4 Medical Oncology, Hôpital Européen Georges Pompidou, APHP.Centre – Université de Paris, Paris, France; Centre de Recherche des Cordeliers, INSERM, Université de Paris, Sorbonne Université, Paris, France, 75015 - Paris/FR
  • 5 Department Of Pathology, Inserm U1085-IRSET, University Hospital, 35000 - Rennes/FR
  • 6 Department Of Urology, University Hospitals Leuven,, 3000 - Leuven/BE
  • 7 Laboratoire D'immuno-oncologie, Gustave Roussy, 94800 - Villejuif/FR
  • 8 Integrative Tumor Immunology And Cancer Immunotherapy, Gustave Roussy - Université Paris-Saclay, 94800 - Villejuif/FR
  • 9 Medical Oncology, INSTITUT CLAUDIUS REGAUD, 31059 - Toulouse/FR
  • 10 Medical Oncology, CHU Bordeaux - Hopital St. André, 33000 - Bordeaux/FR
  • 11 Department Of Medical Oncology, Centre Léon Bérard, Rhones-Alpes/FR
  • 12 Medical Oncology, Centre Eugene - Marquis, 35042 - Rennes/FR
  • 13 Direction De La Recherche Clinique Et De L’innovation (drci), Centre Léon Bérard, 69373 - Lyon/FR
  • 14 Research & Development Department, Unicancer, 94270 - Le Kremlin Bicêtre/FR
  • 15 Laboratory Of Translational Genetics, Vlaams Instituut voor Biotechnologie VIB - KULeuven, 3000 - Leuven/BE
  • 16 Medical Oncology, Gustave Roussy, Université Paris-Saclay, 94805 - Villejuif/FR
  • 17 Medical Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
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Abstract 700O

Background

The NIVOREN GETUG-AFU 26 study reported safety and efficacy of N in metastatic (m-) ccRCC patients (pts) in a “real world setting”. A translational research program including gene expression signatures was launched to identify biomarkers for outcome to N.

Methods

Among the 324 pts included in the NIVOREN translational cohort, RNA-sequencing was performed on 79 FFPE primary ccRCCs. We first evaluated the impact of Teff and Angio signatures on the outcome, based on median mRNA expression values, as described in the IMmotion 150 RCC trial. To better characterize the tumor microenvironment, we performed an unsupervised analysis using MCP-Counter to classify tumors according to their infiltration by 8 immune (I) and 2 stromal (S) (fibroblasts and endothelial) cell populations. Outcomes were the response rate (RR, best response determined by complete or partial response) and PFS.

Results

Angio– and Teff signatures were not predictive of outcomes on N when applied separately. However, combination of these two signatures revealed that the most aggressive tumors Teff-high/Angio-low and Teff-low/Angio-low were significantly associated with RR and PFS (Table).Unsupervised classification identified 5 KIC subtypes (A to E). CD8-high/S-low (KIC C+E) tumors were associated with higher RR and longer PFS compared to I-low/S-low (KIC A), I-low/S-high (KIC B) and I-high/S-high (KIC D) tumors (Table). Principal component analysis showed a similar contribution of KIC stromal cells and the Angio signatures in worst outcome tumors. The KIC classification identified tumor microenvironments linked to good outcomes on N and unraveled the deleterious clinical impact of the potential immunosuppression exerted by neutrophils, fibroblasts and endothelial cells. Table: 700O

RR P-value Fisher exact Median PFS [CI95%] (mo) P-value Log rank
Teff-high/Angio-low 8/17 (47%) 0.01 10.1 [2.7; NE] 0.0005
Teff-high/Angio-high 4/22 (18%) 4.1 [2.6;5.6]
Teff-low/Angio-high 5/16 (31%) 3.2 [2.4;NE]
Teff-low/Angio-low 1/21 (5%) 2.6 [2.1;2.8]
KIC C-E 10/21 (48%) 0.005 11.4 [2.4;NE] 0.03
KIC A-B-D 8/55 (15%) 2.8 [2.7;4.2]

Conclusions

We report for the first time from a prospective trial that Immune high/angiogenesis and stromal low signatures likely predict nivolumab efficacy in m-ccRCC patients.

Clinical trial identification

NCT03013335.

Editorial acknowledgement

Legal entity responsible for the study

Unicancer.

Funding

Institut National du Cancer and Bristol-Myers Squibb.

Disclosure

B. Beuselinck: Honoraria (self), Research grant/Funding (self): Bristol-Myers Squibb ; Honoraria (self): Merck; Honoraria (self): Pfizer; Honoraria (self): Ipsen; Honoraria (self): AstraZeneca. Y. Vano: Honoraria (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Novartis; Honoraria (self): Ipsen; Honoraria (self): Merck; Honoraria (self), Travel/Accommodation/Expenses: MSD; Honoraria (self): Janssen; Honoraria (self): Sanofi; Honoraria (self): Astellas; Honoraria (self), Travel/Accommodation/Expenses: Roche. N. Rioux Leclercq: Travel/Accommodation/Expenses, conference support: Pfizer; Travel/Accommodation/Expenses, conference support: Bristol-Myers squibb; Travel/Accommodation/Expenses, conference support: AstraZeneca. N. Chaput: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Roche; Honoraria (self): Sanofi; Honoraria (self): Cytune Pharma; Honoraria (self): AstraZeneca. C. Chevreau: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Advisory/Consultancy: Novartis. M. Gross Goupil: Honoraria (self), Travel/Accommodation/Expenses: Bristo-Myers Squibb; Honoraria (self), Travel/Accommodation/Expenses: MSD; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Travel/Accommodation/Expenses: Ipsen. A. Fléchon: Honoraria (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Novartis. B. Laguerre: Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Ipsen; Honoraria (self): Roche; Honoraria (self): MSD. B. Escudier: Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Roche; Honoraria (self): Ipsen; Honoraria (self): Eisai; Honoraria (self): EUSA Pharma; Honoraria (self): Oncorena. L. Albiges: Honoraria (institution): Pfizer; Honoraria (institution): Novartis; Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution): Ipsen; Honoraria (institution): Roche; Honoraria (institution): AstraZeneca; Honoraria (institution): Amgen; Honoraria (institution): Astellas; Honoraria (institution): Exelixis; Honoraria (institution): Corvus Pharmaceuticals; Honoraria (institution): Peloton therapeutcis; Honoraria (institution): MSD; Honoraria (institution): Merck. All other authors have declared no conflicts of interest.

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