Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session

4898 - Biomarkers Before and After Nephrectomy of Locally Advanced or Metastatic Renal Cell Carcinoma (RCC) Treated With Everolimus: NEORAD phase 2 trial (PREDICT consortium)

Date

10 Sep 2017

Session

Poster display session

Presenters

Stephane Oudard

Citation

Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371

Authors

S. Oudard1, A. Mejean2, D. Topart3, R. Thuret3, C. Tournigand4, L. Salomon5, A. Thiery-Vuillemin6, G. Guichard6, S. Le Moulec7, A. Houlgatte7, A. Guillot8, N. Mottet9, A. Cessot10, N. Barry-Delongchamps10, R. Elaidi11, S. Turajlic12, C. Swanton13, B. Escudier14, J.J. Patard15, L. Albiges16

Author affiliations

  • 1 Oncology Department, Hopital European George Pompidou, 75015 - Paris/FR
  • 2 Urology, Hopital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris-Descartes, 75015 - Paris/FR
  • 3 Oncology, Hopital Saint-Eloi (Montpellier), 34295 - Montpellier/FR
  • 4 Oncology, Centre hospitalier universitaire Henri-Mondor, 94010 - Créteil/FR
  • 5 Urology, Henri Mondor Hospital, 94000 - Creteil/FR
  • 6 Oncology, CHU Besançon, Hôpital Jean Minjoz, 25030 - Besançon/FR
  • 7 Oncology, HIA Val-de-Grace, 75005 - Paris/FR
  • 8 Oncology, Institute de Cancerologie de la Loire, 42271 - St. Priest en Jarez/FR
  • 9 Urology, CHU University hospital of St Etienne, 42055 - St. Etienne/FR
  • 10 Oncology, Hôpital Cochin, 75679 - Paris/FR
  • 11 Medical Oncology, ARTIC - Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie, 75015 - Paris/FR
  • 12 Oncology, The Francis Crick Institute, London/GB
  • 13 Translational Cancer Therapeutics, Cancer Research UK London Research institute, WC2A 3LY - London/GB
  • 14 -, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 15 Urology, CHU de Bicêtre, 91275 - Le Kremlin Bicetre/FR
  • 16 Medical Oncology, Institut Gustave Roussy, Institut Gustave Roussy, INSERM U753, Villejuif  /FR
More

Resources

Abstract 4898

Background

Although many drugs are available in RCC, we still lack predictive biomarkers of disease recurrence or progression for personalized treatment. NEORAD clinical trial (NCT01715935) was designed to evaluate biomarkers modulation by everolimus (Ev) prior to nephrectomy on several tissue and circulating cells.

Methods

French open-label, exploratory, single-arm, multicenter trial, part of PREDICT consortium. Population: locally-advanced (LA), metastatic (M) RCC. Endpoints: primary: objective clinical benefit (CR, PR, SD upon RECIST 1.1) after 6 weeks neoadjuvant Ev (10 mg daily) prior nephrectomy; secondary: PFS, OS, toxicity. Multi-region sequencing (biopsy and surgery specimens) explored mutational status of genes of interest. After nephrectomy, Ev was reintroduced in M pts until PD or end of 12m follow-up. Treatment was continued until PD or unacceptable toxicity.

Results

25 pts accrued (44 screened) between 05/2012 and 07/2015: LA = 14, M = 11 underwent biopsy at screening for tissue sampling then further nephrectomy. Population (LA/M): clear-cell=13/10, papillary=1/1, median age(y): 60/63, sarcomatoid component: 3 M pts, ECOG-PS: 0=10/4, 1=4/7, extra-renal metastatic sites: bone, lung, nodes, adrenal. Change in renal tumor size between baseline and D42: 0%. In M, Ev was resumed for 8 pts after nephrectomy with 2 PR and 6 SD. PFS (mo): M = 3.1 [1.41; 12.2]. Median follow-up (mo): 17.4 [3.3; 43.2]. PFS at 12 months: LA = 78%, M = 18% Toxicity of Ev was as expected and no adverse event in terms of surgical procedure was observed. Pts with following gene mutations exhibited a poor PFS: SEDT2: HR = 2.54 (0.63 – 10.28), BAP1: HR = 3.19 (0.78 – 13.12), TSC2: HR = 2.37 (0.49 – 11.53); further correlations will be presented at ESMO meeting.

Conclusions

NEORAD was the 1st neoadjuvant study of Ev in RCC. Despite limited number of pts, we generated a large amount of longitudinal data including exome sequencing, circulating biomarkers, angiogenesis and immunity factors. All these data could help decipher mechanisms of resistance, evaluate predictive signatures or add further knowledge to mechanisms involved in mTOR pathways.

Clinical trial identification

NCT01715935

Legal entity responsible for the study

Stéphane Oudard, MD, PhD

Funding

PREDICT Consortium

Disclosure

S. Oudard: Grants and personal fees from Pfizer, personal fees from Novartis, Bristol-Myers Squib, Ipsen, Bayer, outside the submitted work. A. Mejean, J.J. Patard: Fees from Pfizer, Novartis, Bristol-Myers Squib, Ipsen. A. Thiery-Vuillemin: Grants and personal fees from Novartis, during the conduct of the study; grants and personal fees from Pfizer, Bristol-Myers Squib, Ipsen; personal fees from Roche; grants from JNJ, N. Mottet: Fees from Sanofi, Astellas, Janssen. B. Escudier: Honorarium received from: Bristol-Myers Squib, Novartis, Pfizer, Ipsen, Roche, Bayer, Calithera, Acceleron, EUSA, Eisai. L. Albiges: Fees from Pfizer, Novartis, Bristol-Myers Squib, Ipsen, Bayer, Merck. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.