142P - longitudinal exploratory analysis of prior- surgery everolimus circulating and clinical biomarkers in locally advanced and metastatic renal cell ca...

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancer in Adolescents
Renal Cell Cancer
Biomarkers
Genitourinary Cancers
Translational Research
Presenter Reza Elaidi
Citation Annals of Oncology (2017) 28 (suppl_5): v22-v42. 10.1093/annonc/mdx363
Authors R. Elaidi1, D. Helley2, L. Mauge2, C. Badoual3, E. Tartour4, E. Braychenko5, L. Albiges6, B. Escudier7, S. Oudard8
  • 1Medical Oncology - Hôpital Européen Georges Pompidou, ARTIC, 75015 - Paris/FR
  • 2Biologic Haematology, Hopital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris-Descartes, 75015 - Paris/FR
  • 3Medical Oncology, Hopital European George Pompidou, 75015 - Paris/FR
  • 4Biologic Immunology, Hopital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris-Descartes, 75015 - Paris/FR
  • 5Medical Oncology, ARTIC - Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie, 75015 - Paris/FR
  • 6Medical Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 7Medical Oncology, Institut de Cancérologie Gustave Roussy, 94805 - Villejuif/FR
  • 8Immunothérapie Et Traitement Antiangiogénique En Pathologie cancérologique, Hopital European George Pompidou, 75015 - Paris/FR

Abstract

Background

If many drugs are available in RCC, we lack predictive biomarkers of disease recurrence or progression for personalized treatment. Circulating biomarkers (CB) are attractive candidates for disease monitoring. Longitudinal assessment of CB was performed in the NEORAD clinical trial (NCT01715935).

Methods

Locally advanced (LA) and metastatic (M) patients with clear cell or papillary RCC received 6 weeks prior-nephrectomy everolimus (Ev). CB assessed were: angiogenesis factors: VEGF-A, VEGFR-1&2, bFGF, SDF1, PlGF; CEC; CTC; HSC; immune cells: CD45, CD14+VEGFR-1/Tie2, Treg, IL-6. Clinical/histological (CH): ECOG-PS, tumor burden (TB), % necrosis, % sarcomatoid. Exploratory analysis (EA): CB and CH (prior to Ev, D22, D42, 4 weeks post-nephrectomy (+ 4 weeks if Ev resumed in M pts) in PD vs non-PD pts used Bayesian Model Averaging (BMA) and regularized Cox regression (LASSO). Three modeling strategies were compared for robustness.

Results

25 patients were included: LA = 14, M = 11. In LA and M cohorts, respectively 2 and 9 pts exhibited progression during the 12m post-surgery follow-up period. Most important predictors upon EA (by order): tumor burden, VEGF-A, LA/M, VEGFR-2, % necrosis, IL-6, VEGFR-1, age, PlGF. Higher TB at baseline and % necrosis were associated with increased risk of 6m post-nephrectomy progression. TB, IL-6, VEGF-A, VEGFR-1&2 exhibited nonlinear relationships suggesting complex underlying pathophysiological mechanisms involved in response to Ev, and are currently explored. Reduced VEGFR-2 at D42 was associated with worse PFS in both cohorts. Upon BMA and LASSO, % necrosis and TB were among the most retrieved predictors prior to nephrectomy, whereas CD45 and CD34 + 45-146+ at 4 weeks post-nephrectomy were the best CB predictors. No significant change in monocyte populations and in Treg was observed.

Conclusions

VEGF related CB, TB and % necrosis were the best candidates to discriminate PD- vs non-PD in LA and M pts. Extensive analysis of data collected using robust non-linear models could contribute to improve our understanding of mechanisms involved and suggest predictive biomarkers to be validated.

Clinical trial identification

NCT01715935

Legal entity responsible for the study

ARTIC

Funding

Novartis

Disclosure

All authors have declared no conflicts of interest.