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gynecological cancers
966O BRIVANIB (B) IN ADVANCED OVARIAN CANCER (OC): SUBSET
RESULTS OF A PHASE 2 RANDOMIZED DISCONTINUATION
TRIAL (RDT)
S.B. Kaye 1 , L.L. Siu 2 , J. Jassem 3 , J. Medioni 4 , P. M.M.B. Soetekouw 5 ,
S. Slater 6 , C. M. Rudin 7 , G.K. Schwartz 8 , M. De Jonge 9 ,P.O’Dwyer 10 ,
C. Baudelet 11 , A. Chen 12 , M. J. Ratain 13
1 Royal Marsden Hospital and Institute of Cancer Research, Sutton, UNITED
KINGDOM, 2 Department of Medical Oncology, Princess Margaret Hospital,
Toronto, CANADA, 3 Oncology and Radiotherapy, Medical University of Gdansk,
Gdansk, POLAND, 4 Département d’Oncologie Médicale, Hôpital Européen
Georges Pompidou, Paris, FRANCE, 5 Division of Medical Oncology, Maastricht
University Medical Center, Maastricht, NETHERLANDS, 6 Department of Medical
Oncology, Beatson West of Scotland Cancer Center, Glasgow, UNITED
KINGDOM, 7 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins
University, Baltimore, MD, UNITED STATES OF AMERICA, 8 Melanoma and
Sarcoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY,
UNITED STATES OF AMERICA, 9 Department of Medical Oncology, Erasmus
University Medical Center, Rotterdam, NETHERLANDS, 10 Abramson Cancer
Center, University of Pennsylvania, Philadelphia, PA, UNITED STATES OF
AMERICA, 11 Research and Development, Brstol-Myers Squibb, Braine-l’Alleud,
BELGIUM, 12 Research and Development, Bristol-Myers Squibb, Wallingford, CT,
UNITED STATES OF AMERICA, 13 Department of Medicine, University of
Chicago, Chicago, IL, UNITED STATES OF AMERICA
Background: Brivanib (B) is an oral once daily selective dual inhibitor of FGF
and VEGF signaling with preclinical activity against various tumor types. An
RDT assessed B in pts with advanced solid tumors; data showing activity in
sarcoma pts were reported previously, and data for the OC pts are presented
here.
Methods: OC pts progressing after previous treatment received open-label B 800 mg
QD for a 12-wk lead-in period and were assessed by CT/MRI. Pts with complete
(CR) or partial response (PR) continued on open-label B, those with progressive
disease (PD) went off study. Pts with stable disease (SD) were randomized 1:1 to B
or placebo (P) until PD or intolerance. Pts with PD on P could crossover to
open-label B. Endpoints included progression-free survival (PFS) in randomized
pts, objective response rate (ORR), disease control rate (DCR = ORR + SD), and
safety.
Results: One hundred twenty-six pts (63% with >3 prior systemic regimens; 88%
FGF2 + by IHC) entered 12-wk lead-in and received B. At wk 12, 12 pts had PR and
43 pts had SD (ORR 10%; DCR 44%). Three of 18 pts pretreated with bevacizumab
(BEV) achieved PR at wk 12. After 12 wks, 49 continued on the study, 10 with PR
remained on open-label B; and 39 were randomized to either B (n = 19) or P (n =
20). Two pts with PR were randomized in error. Among randomized pts (n = 39),
median PFS was 4 mo for B vs 2 mo for P with HR of 0.54 (90% CI: 0.28-1.03;
p = 0.11). Among randomized FGF2 + pts (n = 36), HR was 0.56 (90% CI:
0.29-1.07; p = 0.14). In the randomized phase, 3 additional pts achieved PR
(overall population: 15 PRs; ORR 12%). The most common (≥5%) grade ≥3 AEs
were increased ALT (20%) and AST (14%), fatigue (12%), hyponatremia (9%),
asthenia (7%), diarrhea (7%), hypertension (7%), abdominal pain (6%), and
decreased appetite (6%). Discontinuation due to treatment-related AE occurred in
13% of pts.
Conclusions: The observed PFS prolongation with B vs P, ORR and DCR in this
RDT indicate clinical activity of B in pts with heavily pretreated OC, including those
with prior BEV. The high frequency of FGF2 + pts precluded the assessment of FGF2
as a predictive biomarker. The safety profile was acceptable. These results support
further investigation of B in OC, potentially in pts with prior BEV.
Disclosure: S.B. Kaye: Consultant for Astra Zeneca, Clovis, GSK, J&J, Pfizer Roche
advisory boards Received payment from Roche for development of educational
presentations L. Siu: Received research funding from Bristol-Myers Squibb J.
Jassem: Advisory Board Member for Bristol-Myers Squibb C.M. Rudin:
Consultancy for Oncothyreon P.J. O’Dwyer: Research funding and honorarium
from Bristol-Myers Squibb Company. C. Baudelet: Employment and stock
ownership of Bristol-Myers Squibb Company. A. Chen: Employment and stock
ownership of Bristol-Myers Squibb Company. M.J. Ratain: Research funding
from Bristol-Myers Squibb Company All other authors have declared no
conflicts of interest.
Annals of Oncology 23 (Supplement 9): ix319–ix333, 2012
doi:10.1093/annonc/mds401
967O UPDATED OVERALL SURVIVAL ANALYSIS IN OCEANS, A
RANDOMIZED PHASE 3 TRIAL OF GEMCITABINE (G) +
CARBOPLATIN (C) AND BEVACIZUMAB (BV) OR PLACEBO (PL)
FOLLOWED BY BV OR PL IN PLATINUM-SENSITIVE
RECURRENT EPITHELIAL OVARIAN (ROC), PRIMARY
PERITONEAL (PPC), OR FALLOPIAN TUBE CANCER (FTC)
C. Aghajanian 1 , L.R. Nycum 2 , B. Goff 3 , H. Nguyen 4 , A. Husain 5 , S.V. Blank 6
1 Gynecologic Medical Oncology Service Memorial Sloan-Kettering Cancer
Center New York NY UNITED STATES OF AMERICA, 2 Department of Obstetrics
Gynecology Forsyth Regional Cancer Center Winston-Salem NC UNITED
STATES OF AMERICA, 3 Department of Obstetrics Gynecology University of
Washington School of Medicine Seattle WA UNITED STATES OF AMERICA,
4 Biostatistics Genentech Inc. South San Francisco CA UNITED STATES OF
AMERICA, 5 Avastin Ovarian Cancer Program Genentech Inc. South
San Francisco CA UNITED STATES OF AMERICA, 6 Division of Gynecologic
Oncology NYU School of Medicine New York NY UNITED STATES OF AMERICA
Background: In OCEANS, BV in combination with GC resulted in a statistically
significant and clinically meaningful improvement in PFS in patients (pts) with
platinum-sensitive (Plat-S) ROC (median PFS, 12.4 vs 8.4 months; HR = 0.484;
P < .0001). These results were supported by the overall response rate (ORR), duration
of response (DOR), and independent review committee (IRC) analyses. At the time
of the final PFS analysis, the OS data were still not mature. Additional OS updates
have been performed; here we present the 3rd interim OS analysis.
Methods: Eligibility criteria included first recurrence of Plat-S OC, PPC, or FTC with
an ECOG PS of 0 or 1, no prior BV or chemotherapy for ROC, and measurable
disease. Pts were randomized 1:1 to arm A: GC (G [1000 mg/m2, days 1 and 8] and
C [AUC 4, day 1], q3w for 6–10 cycles) + concurrent PL (q3w), followed by PL until
disease progression (PD) or unacceptable toxicity; or arm B: GC + concurrent BV
(15 mg/kg q3w), followed by BV until PD or unacceptable toxicity. The primary end
point was investigator-assessed PFS by RECIST. Secondary end points included ORR,
OS, DOR, and safety. The 3rd interim OS analysis was conducted with a data cutoff
date of March 30, 2012.
Results: As of the data cutoff date, 286 events (59% of pts) had occurred. There was no
difference in OS between the arms, with an HR of 0.960 (95% CI, 0.760–1.214; log-rank
P = 0.736). With a median follow-up of 42 months, median OS was 33.7 months in the
GC + PL arm and 33.4 months in the GC + BV arm. There was no difference in the
number of grade 5 treatment-emergent adverse events between arms (1 in each), the
number of deaths was balanced between arms, and the cause of death in the majority of
cases was PD in both arms. 89% and 86% of pts received subsequent therapy (including
BV in 39% and 22%) in the PL and BV arms, respectively.
Conclusions: These data provide assurance that there is no detriment to OS with
the addition of BV in this setting, and supports the positive benefit:risk ratio of the
GC + BV regimen in significantly improving PFS in patients with platinum-sensitive
ROC.
Disclosure: L.R. Nycum: Dr. Nycuum was a member of the Avastin-Ovary advisory
board for Genentech for a contract of 1 year. The contract ended the end of March
2012. H. Nguyen: Hoa Nguyen is an employee of Genentech and owns stock in
Roche. A. Husain: Dr. Husain is an employee of Genentech and holds stock
ownership (Roche). All other authors have declared no conflicts of interest.
969PD NATURAL HISTORY OF SEROUS OVARIAN CARCINOMA:
HIGH GRADE VERSUS LOW GRADE AND CARCINOMAS
WITH BRCA MUTATIONS
S. Ayers 1 , T.T. Tun 1 , N. Mescallado 1 , A. Wright 1 , D.G.R. Evans 2 , A. Clamp 1 ,
G.C. Jayson 1 , J. Hasan 1
1 Medical Oncology, The Christie NHS Foundation Trust, Manchester, UNITED
KINGDOM, 2 Regional Genetic Service, St Mary’s Hospital, Manchester, UNITED
KINGDOM
Serous carcinomas are the commonest histological subtype of epithelial ovarian
cancer (EOC) and associated with BRCA mutations. In this study we analysed
presentation and treatment-related outcomes of patients with high-grade(HGSC) and
low-grade serous carcinomas (LGSC) and their relationship with BRCA mutations.
Study design: A retrospective cohort study was carried out. Patients diagnosed with
serous ovarian carcinoma from 2005-2010 were identified. A separate database was
accessed to identify BRCA carriers ever treated at the Christie Hospital, UK.
Individual patient data was analysed.
Results: 391 patients were identified including 151 with BRCA mutations.
Preliminary data on 303 cases is discussed. Mature data will be presented at the
© European Society for Medical Oncology 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
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