C121
Maintenance therapy following chemotherapy of relapsed ovarian cancer: a randomised placebo-controlled phase II trial with the angiogenesis inhibitor BIBF 1120
Gordon Rustin1, Jonathan Ledermann2, Alan Hackshaw3, Stan Kaye4, Gordon Jayson5, Hani Gabra6, Lindsey James3, Susan Bell7, Graham Temple7
1Mount Vernon Cancer Centre, Northwood, Middlesex, UK, 2University College London Hospitals, UK, 3CR-UK & University College London Cancer Trials Centre, UK, 4Royal Marsden Hospital, London, UK, 5Christie Hospital, London, UK, 6Hammersmith Hospital, London, UK, 7Boehringer Ingelheim Ltd, Bracknell, UK
Background
A novel trial design of maintenance therapy was used to evaluate BIBF1120, a triple angiokinase inhibitor targeting VEGFR, PDGFR and FGFR involved in the formation of blood vessels.
Method
Continuous BIBF1120 (250 mg, oral, twice daily) for up to 36 weeks (wk) was compared with placebo in a randomised double-blind trial. To be eligible patients had to have responded to their last chemotherapy, which had to be at least second line . The primary endpoint was progression-free survival at 36 weeks.
Results
83 pts were randomised (43 BIBF1120; 40 placebo). All had responded to the prior relapse chemotherapy according to GCIG criteria. Treatment-free interval before prior chemotherapy was < 6 months for 41% and 6-12 months for 59% of pts. Median treatment duration was 116 days (d), range, 2-281d (BIBF 1120) and 101 d, 2-239d (placebo). Five BIBF 1120 pts completed 36 wk of treatment vs 0 placebo pts. The 36-wk PFS rates (95% confidence interval [CI]) were 14.3% (95 % CI 3.7-24.9) for BIBF1120 and 5.0 % ( 95% CI 0-11.8) for placebo. Although the trial was not powered for a direct comparison, the PFS hazard ratio was 0.68 (95% CI 0.44-1.07). Grade 3 & 4 adverse events (AE) were seen in 54 & 7% (BIBF1120) and 25 & 3% (placebo) of pts. Elevated liver enzymes occurred in 43% (BIBF1120), leading to drug discontinuation in 2 pts vs. 6.3% (placebo).
Conclusion
Our trial suggests that maintenance with BIBF1120 could delay disease progression in ovarian cancer pts who had previously responded to chemotherapy. A large phase III trial is needed to confirm the efficacy of this drug
