880P - Biomarkers Before and After Nephrectomy of Locally Advanced or Metastatic Renal Cell Carcinoma (RCC) Treated With Everolimus: NEORAD phase 2 trial...

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Genitourinary Cancers
Translational Research
Presenter 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
  • 1Oncology Department, Hopital European George Pompidou, 75015 - Paris/FR
  • 2Urology, Hopital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris-Descartes, 75015 - Paris/FR
  • 3Oncology, Hopital Saint-Eloi (Montpellier), 34295 - Montpellier/FR
  • 4Oncology, Centre hospitalier universitaire Henri-Mondor, 94010 - Créteil/FR
  • 5Urology, Henri Mondor Hospital, 94000 - Creteil/FR
  • 6Oncology, CHU Besançon, Hôpital Jean Minjoz, 25030 - Besançon/FR
  • 7Oncology, HIA Val-de-Grace, 75005 - Paris/FR
  • 8Oncology, Institute de Cancerologie de la Loire, 42271 - St. Priest en Jarez/FR
  • 9Urology, CHU University hospital of St Etienne, 42055 - St. Etienne/FR
  • 10Oncology, Hôpital Cochin, 75679 - Paris/FR
  • 11Medical Oncology, ARTIC - Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie, 75015 - Paris/FR
  • 12Oncology, The Francis Crick Institute, London/GB
  • 13Translational Cancer Therapeutics, Cancer Research UK London Research institute, WC2A 3LY - London/GB
  • 14-, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 15Urology, CHU de Bicêtre, 91275 - Le Kremlin Bicetre/FR
  • 16Medical Oncology, Institut Gustave Roussy, Institut Gustave Roussy, INSERM U753, Villejuif  /FR

Abstract

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.