966O - Brivanib (B) in advanced ovarian cancer (OC): subset results of a phase 2 randomized discontinuation trial (RDT)

Date 30 September 2012
Event ESMO Congress 2012
Session Gynecological cancer
Topics Cytotoxic agents
Ovarian Cancer
Therapy
Biological therapy
Presenter Stanley Kaye
Authors S.B. Kaye1, L. Siu2, J. Jassem3, J. Medioni4, P.M.M.B. Soetekouw5, S. Slater6, C.M. Rudin7, G.K. Schwartz8, M. de Jonge9, P.J. O'Dwyer10, C. Baudelet11, A. Chen12, M. Ratain13
  • 1Dept Of Medicine, Royal Marsden Hospital and Institute of Cancer Research, Sutton/UK
  • 2Dept Of Medical Oncology, Princess Margaret Hospital, CA-M5G 2M9 - Toronto/CA
  • 3Oncology And Radiotherapy, Medical University of Gdansk, PL-80-211 - Gdansk/PL
  • 4Dept. Medical Oncology, Hopital European George Pompidou, 75015 - Paris/FR
  • 5Medical Oncology Dept., Maastricht University Medical Center, NL-6229 HX - Maastricht/NL
  • 6Department Of Medical Oncology, Beatson West of Scotland Cancer Center, Galsgow/UK
  • 7Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore/US
  • 8Melanoma And Sarcoma Service, Memorial Sloan-Kettering Cancer Center, New York/US
  • 9Department Of Medical Oncology, Erasmus University Medical Center, Rotterdam/NL
  • 10Abramson Cancer Center, University of Pennsylvania, Philadelphia/US
  • 11Research And Development, Brstol-Myers Squibb, Braine-l'Alleud/BE
  • 12Research And Development, Bristol-Myers Squibb, Wallingford/US
  • 13Department Of Medicine, University of Chicago, Chicago/US

Abstract

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.