A phase II study of cediranib (AZD2171) in recurrent or persistent ovarian, peritoneal or fallopian tube cancer: Final results of a PMH, Chicago and California consortia trial

Abstract

5521 Background: VEGF is over-expressed in human ovarian tumours and this is associated with a poor prognosis. Cediranib (AZD2171) is a novel, orally-administered, highly potent inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ and c-kit. A two-stage, multicentre phase 2 clinical trial was initiated to evaluate the activity of cediranib in patients (pts) with recurrent ovarian, peritoneal or fallopian tube cancer. Methods: Pts with ECOG ≤ 2 and adequate organ function were eligible. Prior chemotherapy up to one line was permitted. The initial starting dose of cediranib was reduced from 45 mg orally daily (od) to 30 mg od continuously because of toxicity. The primary endpoint was objective response rate and rate of progression-free survival (PFS) at 16 weeks, with response evaluated every 8 weeks. This study was stratified into two separate arms: platinum-sensitive (pl-s) and platinum-resistant (pl-r) pts. 60 pts were enrolled; follow up is available for 154 cycles of treatment given to 46 pts. Results: 49 pts had ovarian, 8 peritoneal, and 3 fallopian tube cancer. 26 pts were pl-s and 34 pts were pl-r. Median age: 58 years (range 31–87), ECOG 0/1/2:30/25/5 pts. Median number of months of treatment: 3 (range 1–9). The most frequent adverse events (AEs) were fatigue (85%), diarrhea (80%), hypertension (72%), anorexia (57%). Hypertension (33%) and fatigue (20%) were the most frequent grade 3+ AEs. 16 pts required dose reduction to 30 mg (8) and 20 mg (8). Reasons for stopping study treatment were (pl-s/pl-r): PD (12/9), AEs (3/6), investigator decision (1/0) and patient withdrawal (1/2). Excluding patients who are too early for tumor assessment (9 pl-s/10 pl-r), response and prolonged SD rate was 41%/29% for pl- s and pl-r pts respectively. In the pl-s group, there have been 2 confirmed PRs and 1 unconfirmed PR while one unconfirmed PR was observed in the pl-r arm. The median time to progression (TTP) and median survival time for all pts was 4.1 months (95% CI 3.4–7.6) and 11.9 months (95% CI: 9.9-not reached) respectively with no significant differences between groups. Conclusions: Cediranib is well tolerated at 30 mg od and shows significant activity in recurrent ovarian cancer. No significant financial relationships to disclose.