783O - Randomized phase II study of first-line everolimus (EVE) + bevacizumab (BEV) versus interferon alfa-2a (IFN) + BEV in patients (pts) with metastatic...

Date 01 October 2012
Event ESMO Congress 2012
Session Genitourinary tumors, renal cancer
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Presenter Alain Ravaud
Authors A. Ravaud1, C. Barrios2, O. Anak3, D. Pelov4, A. Louveau5, B. Alekseev6, T. M-H7, S.S. Agarwala8, S. Yalcin9, B. Melichar10
  • 1Bordeaux University, 33075 - Bordeaux/FR
  • 2PUCRS School of Medicine, Porto Alegre/BR
  • 3Oncology Clinical Development, Novartis Pharma AG, Basel/CH
  • 4Oncology, Novartis Pharmaceuticals Corporation, Florham Park/US
  • 5Oncology, Novartis Pharma S.A.S., Paris/FR
  • 6Oncourological Department, Moscow Hertzen Oncology Institute, Moscow/RU
  • 7Oncology, OncoCare Cancer Centre, Singapore/SG
  • 8Cancer Center, St. Luke's Hospital & Health Network, 18015 - Bethlehem/US
  • 9Medical Oncology, Hacettepe University Institute of Oncology, TR-06100 - Ankara/TR
  • 10Oncology, Palacky Univeristy Medical School and Teaching Hospital, Olomouc/CZ

Abstract

Background

Study results demonstrated that IFN augments BEV activity and improves median PFS in pts with mRCC. Thus, combination BEV + IFN is a standard first-line treatment option for mRCC. Combining BEV with the mTOR inhibitor EVE may be an efficacious and well-tolerated treatment option. The open-label, phase II RECORD-2 trial compared first-line EVE + BEV and IFN + BEV in mRCC. Patients and methods: Therapy-naive pts with clear cell mRCC and prior nephrectomy were randomized 1:1 to BEV 10 mg/kg IV every 2 weeks with either EVE 10 mg oral daily or IFN (9 MIU SC 3 times/week, if tolerated). Tumour assessments were every 12 weeks. Primary objective was treatment effect on progression-free survival (PFS) per central review based on an estimate of the chance of a subsequent phase III trial success (50% threshold for phase II success).

Results

In EVE + BEV (n = 182) and IFN + BEV (n = 183) arms, median age was 60/60 years, 76/72% of pts were men, MSKCC risk was favourable/intermediate/poor in 36/57/7% and 36/57/7% of pts, and 43/46% of pts had >2 organs involved, respectively. For EVE + BEV and IFN + BEV, median treatment duration was 8.5/8.3 months, respectively; 23/26% of pts discontinued due to AEs. In EVE + BEV and IFN + BEV arms, median PFS by central review was 9.3/10.0 months (HRIFN/EVE, 0.91; 95% CI, 0.69-1.19; P =0.485), respectively; probability of subsequent phase III success was 5.1%. Results of central and local PFS analysis were consistent. Objective response rate was 27/28% in EVE + BEV and IFN + BEV arms, respectively. Median overall survival (OS) was not reached in the EVE + BEV arm and was 25.9 months (95% CI: 21.1, 30.2) in the IFN + BEV arm. Most frequent AEs (%) were stomatitis (63), proteinuria (49), diarrhoea (39), hypertension (38), and epistaxis (35) in EVE + BEV arm and decreased appetite (45), fatigue (41), proteinuria (37), and pyrexia (35) in IFN + BEV arm.

Conclusions

In RECORD-2, PFS and tolerability were similar for first-line EVE + BEV and IFN + BEV. Final OS analysis will occur after 2-year follow-up.

Disclosure

A. Ravaud: Alain Ravaud is a member of global, European, and/or French boards on urological tumors for Pfizer, Novartis, GlaxoSmithKline, Bayer-Schering, and Dendreon, and has received institutional grant support from Pfizer, Novartis, and Roche.

Ö. Anak: Ozlem Anak is an employee of Novartis Pharma AG.

D. Pelov: Diana Pelov is an employee of Novartis Pharmaceuticals Corporation.

A. Louveau: Anne-Laure Louveau is an employee of Novartis Pharma S.A.S.

T. M-H: Tay M-H is a speaker for an advisory board for Novartis Pharmaceuticals Corporation.

B. Melichar: Bohuslav Melichar has received honoraria from Novartis and Roche and served on an advisory board for Roche.

All other authors have declared no conflicts of interest.