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Poster Discussion session - Genitourinary tumours, non prostate

1957 - Tumor molecular characteristics in patients (pts) with International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) good (G) and intermediate/poor (I/P) risk

Date

20 Oct 2018

Session

Poster Discussion session - Genitourinary tumours, non prostate

Topics

Pathology/Molecular Biology

Tumour Site

Renal Cell Cancer

Presenters

Benoit Beuselinck

Citation

Annals of Oncology (2018) 29 (suppl_8): viii303-viii331. 10.1093/annonc/mdy283

Authors

B. Beuselinck1, A.T.L. Verbiest2, G. Couchy3, S. Job4, A. de Reyniès4, S. Caruso3, V. Verkarre5, N. Rioux-Leclercq6, P. Schöffski1, Y. Vano7, R. Elaidi8, E. Lerut9, M. Albersen10, S. Oudard11, J. Zucman-Rossi12

Author affiliations

  • 1 General Medical Oncology, University Hospitals Leuven, 3000 - Leuven/BE
  • 2 Laboratory Of Medical Oncology, KU Leuven, 3000 - Leuven/BE
  • 3 U1162, INSERM, 75010 - Paris/FR
  • 4 Biostatistique, La Ligue Contre Le Cancer, 75014 - Paris/FR
  • 5 Pathologie, Hôpital Necker Enfants malades, 75015 - Paris/FR
  • 6 Pathology, CHU PONTCHAILLOU, RENNES/FR
  • 7 Oncologie Médicale, HEGP, 75015 - Paris/FR
  • 8 Oncologie Médicale, ARTIC - Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie, 75015 - Paris/FR
  • 9 Pathology, University Hospitals Leuven, 3000 - Leuven/BE
  • 10 Urology, University Hospitals Leuven, 3000 - Leuven/BE
  • 11 Immunothérapie Et Traitement Antiangiogénique En Pathologie cancérologique, Hopital European George Pompidou, 75015 - Paris/FR
  • 12 Oncologie Médicale, Université Paris Descartes, 75006 - Paris/FR
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Resources

Abstract 1957

Background

In advanced clear cell renal cell carcinoma (ccRCC), Checkmate214 demonstrated superior response rates (RR) and progression-free survival (PFS) with ipilimumab/nivolumab (IPI/NIVO) in IMDC I/P-risk pts and with sunitinib (SUN) in G-risk pts. We aimed to study the underlying biologic mechanisms.

Methods

We have recently proposed four molecular ccRCC subtypes: ccrcc2-tumors, characterized by a pro-angiogenic gene signature, respond well to SUN, while ccrcc1- and 4-tumors are intermediate and poor responders to SUN. We analyzed our ccRCC databank and correlated the IMDC prognostic score at start of systemic therapy with mRNA-expression of genes involved in angiogenesis (HIF1A/2A, VEGFA, VEGFR1/2/3) and in the immunosuppressive microenvironment (PD1, PDL1/2, LAG3, CD8A, CD3G, IFNG, CXCL13) and with the molecular ccrcc1-4 classification of the primary tumor.Table: 869PD

IMDC G-riskIMDC I/P-riskp (+difference in %)Test
MOLECULAR SUBTYPESccrcc114% (3/22)34% (47/140)0.08Fisher exact
ccrcc277% (17/22)41% (59/140)0.002
ccrcc39% (2/22)5% (7/140)0.35
ccrcc40% (0/22)20% (28/140)0.02
PRO-ANGIOGENIC GENE EXPRESSION (deltadeltaCT)HIF1A0.820.630.21 (+29%)Student’s test
HIF2A1.220.780.03 (+57%)
VEGFA7.104.260.07 (+67%)
VEGFR13.061.530.02 (+100%)
VEGFR21.370.600.009 (+128%)
VEGFR31.070.710.03 (+52%)
OUTCOME ON FIRST-LINE VEGFR-TKI (n = 151)RR63%40%0.08Fisher exact
PFS (months)25100.03

Results

162 pts were included (14% IMDC G-, 65% I- and 21% P-risk). The majority of G-risk pts (77%) had ccrcc2-tumors. ccrcc1- (14%) and ccrcc4-tumors (0%) were less frequent. In I/P-risk pts, ccrcc2-tumors were less frequent (41%), and ccrcc1- (34%) and ccrcc4-tumors (20%) more frequent. mRNA expression of HIF2A, VEGFR1, -2 and -3 was higher in G-risk pts compared to I/P-risk pts. Identical expression of immune related genes was found across all IMDC subgroups.

Conclusions

The majority of IMDC G-risk ccRCCs pts have ccrcc2-tumors. G-risk pts display a higher expression of the VEGF-dependent pro-angiogenic pathway, compared to I/P-risk pts. This may explain the increased benefit of SUN over IPI/NIVO in G-risk pts in Checkmate214.

Clinical trial identification

Legal entity responsible for the study

University Hospitals Leuven.

Funding

La Ligue Contre le Cancer France.

Editorial Acknowledgement

Disclosure

B. Beuselinck: Speeker's fee, Research grant: Pfizer P. Schöffski: Institutional travel grant: Pfizer. S. Oudard: Speeker's fee: Pfizer All other authors have declared no conflicts of interest.

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