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 Anticancer Agents
Renal Cell Cancer
Therapy
Biological Therapy
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.