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genitourinary tumors, non-prostate
783O RANDOMIZED PHASE II STUDY OF FIRST-LINE EVEROLIMUS
(EVE) + BEVACIZUMAB (BEV) VERSUS INTERFERON ALFA-2A
(IFN) + BEV IN PATIENTS (PTS) WITH METASTATIC RENAL
CELL CARCINOMA (MRCC): RECORD-2
A. Ravaud 1 , C. Barrios 2 , Ö. Anak 3 , D. Pelov 4 , A. Louveau 5 , B. Alekseev 6 ,
T. M-H 7 , S.S. Agarwala 8 , S. Yalcin 9 , B. Melichar 10
1 Medical Oncology, Bordeaux University, Bordeaux, FRANCE, 2 Department of
Medicine, PUCRS School of Medicine, Porto Alegre, BRAZIL, 3 Oncology Global
Development, Novartis Pharma AG, Basel, SWITZERLAND, 4 Oncology, Novartis
Pharmaceuticals Corporation, Florham Park, NJ, UNITED STATES OF AMERICA,
5 Oncology, Novartis Pharma S.A.S., Paris, FRANCE, 6 Oncourological
Department, Moscow Hertzen Oncology Institute, Moscow, RUSSIAN
FEDERATION, 7 Oncology, OncoCare Cancer Centre, Singapore, SINGAPORE,
8 Cancer Center, St. Luke’s Hospital & Health Network, Bethlehem, PA, UNITED
STATES OF AMERICA, 9 Medical Oncology, Hacettepe University Institute of
Oncology, Ankara, TURKEY, 10 Department of Oncology, Palacky Univeristy
Medical School and Teaching Hospital, Olomouc, CZECH REPUBLIC
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.
784O CLINICAL ACTIVITY AND SAFETY OF ANTI-PROGRAMMED
DEATH-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) IN
PATIENTS (PTS) WITH PREVIOUSLY TREATED, METASTATIC
RENAL CELL CARCINOMA (MRCC)
D.F. McDermott 1 , C.G. Drake 2 , M. Sznol 3 , T.K. Choueiri 4 , J.D. Powderly 5 ,
D.C. Smith 6 , J.M. Wigginton 7 , G. Kollia 8 , A. Gupta 9 , M.B. Atkins 10
1 Division of Hematology/Oncology, Beth Israel Deaconess Medical Center,
Boston, MA, UNITED STATES OF AMERICA, 2 Department of Urology, Sidney
Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore,
MD, UNITED STATES OF AMERICA, 3 Section of Medicine Oncology, Yale
Cancer Center, New Haven, CT, UNITED STATES OF AMERICA, 4 Lank Center
for Genitourinary Oncology, Dana-Farber Cancer Institute/Brigham and Women’s
Hospital, Harvard Medical School, Boston, MA, UNITED STATES OF AMERICA,
5 Oncology, Carolina Bio-Oncology Institute, Huntersville, NC, UNITED STATES
OF AMERICA, 6 Department of Internal Medicine, University of Michigan, Ann
Arbor, MI, UNITED STATES OF AMERICA, 7 Discovery Medicine-clinical
Oncology, Bristol-Myers Squibb, Princeton, NJ, UNITED STATES OF AMERICA,
8 Biostatistics and Data Management, Bristol-Myers Squibb, Princeton, NJ,
UNITED STATES OF AMERICA, 9 Discovery Medicine, Immuno-oncology,
Bristol-Myers Squibb, Princeton, NJ, UNITED STATES OF AMERICA, 10 Internal
Medicine, Georgetown Lombardi Comprehensive Cancer Center, Washington
DC, UNITED STATES OF AMERICA
Purpose: BMS-936558 is a fully human monoclonal antibody that blocks the PD-1
co-inhibitory receptor expressed by activated T cells. In the initial portion of a phase
1 study, BMS-936558 showed promising activity in pts with various solid tumors,
including mRCC. Accrual was expanded to better characterize antitumor, safety, and
dose effects.
Methods: Pts with RCC were treated with BMS-936558 IV q2wk at 10 mg/kg
initially, followed by additional pts at 1 mg/kg. Pts received up to 12 cycles (4 doses/
cycle) of treatment or until unacceptable toxicity, confirmed progressive disease, or
complete response (CR). Clinical activity was assessed by RECIST v1.0.
Results: As of Feb 24, 2012, 34 mRCC pts had been treated at 1 mg/kg (n = 18) or
10 mg/kg (n = 16). ECOG performance status was 0 in 13 pts and 1 in 21 pts. The
number of prior therapies was 1 (n = 10), 2 (n = 9), or ≥3 (n = 15), and included
prior immunotherapy (n = 20) or antiangiogenic therapy (n = 25); 32/34 pts had
prior nephrectomy. Sites of metastatic disease included lymph node (n = 28), liver
(n = 9), lung (n = 30), and bone (n = 10). Median duration of therapy was 32 wks
(range 4 − 97.3 wks). The incidence of grade 3 − 4 related adverse events was 18%
and included hypophosphatemia (6%), elevated ALT (3%), and cough (3%); there
were no drug-related deaths among mRCC pts. Clinical activity (response or
prolonged stable disease) was observed at both doses (Table). Two pts had a
persistent reduction in target lesion tumor burden in the presence of new lesions and
were not categorized as responders. There were responses in all sites of disease.
Conclusions: BMS-936558 is well tolerated and has durable clinical activity in pts
with previously treated, mRCC. Additional long-term follow-up data will be reported.
Dose
(mg/kg)
No.
pts a
ORR
No. pts (%)
[95% CI]
1 17 4 (24)
[7 − 50]
10 16 5 (31)
[11 − 59]*
Annals of Oncology 23 (Supplement 9): ix258–ix293, 2012
doi:10.1093/annonc/mds399
Response
duration
(months)
17.5 + ,
9.2 + , 9.2,
5.6+
22.3 + ,
21.7 + ,
12.9, 12.0,
8.4
SD ≥24 wk
No. pts (%)
[95% CI]
4 (24)
[7 − 50]
5 (31)
[11 − 59]
PFSR at
24 wk (%)
[95% CI]
47 [23 − 71]
67 [43 − 91]
a Response-evaluable pts dosed by 07/01/2011 *1 CR ORR = objective response rate
([{CR + PR} ÷ n] × 100); SD = stable disease; PFSR = progression-free survival rate.
Disclosure: D.F. McDermott: Advisory Role: Bristol-Myers Squibb (myself, Ad board
participation). C.G. Drake: Consultant or Advisory Role: Bristol-Myers Squibb,
Dendreon Inc., and Amplimmune Inc. (myself, compensated). Stock Ownership:
Amplimmune (myself). Other Renumerations: Patents Licensed, Bristol-Myers
Squibb (myself). M. Sznol: Consultant or Advisory Role: Bristol-Myers Squibb
(myself, compensated). Research Funding: Bristol-Myers Squibb (clinical trials
funding, myself). T.K. Choueiri: Consultant or Advisory Role: GlaxoSmithKline,
Aveo, Novartis and Pfizer (myself, compensated). Research Funding: Pfizer (myself).
© European Society for Medical Oncology 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
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