A randomised placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer

McNeish, I.A. et al. (2014) A randomised placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer. Annals of Oncology, 25(10), pp. 1988-1995. (doi: 10.1093/annonc/mdu363)

Abstract

Background: We investigated whether the Src inhibitor saracatinib (AZD0530) improved efficacy of weekly paclitaxel in platinum-resistant ovarian cancer.<p></p> Patients and Methods: Patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer were randomised 2:1 to receive eight-week cycles of weekly paclitaxel (wPxl; 80 mg/m2/week x6 with 2 week break) plus saracatinib (S; 175 mg od) or placebo (P) continuously, starting 1 week prior to wPxl, until disease progression. Patients were stratified by taxane-free interval (<6 months [m] vs. ≥6 m/no prior taxane). The primary endpoint was progression-free survival (PFS) rate at 6 m. Secondary endpoints included overall survival (OS) and response rate (RR).<p></p> Results: 107 patients, median age 63 years, were randomised. 43 (40%) had received >2 lines of prior chemotherapy. The 6 month PFS rate was 29% (wPxl+S) vs. 34% (wPxl+P) (p=0.582). Median PFS was 4.7 vs. 5.3 months (HR 1.00, 95% CI 0.65, 1.54; p=0.99). RR (complete+partial) was 29% (wPxl+S) vs. 43% (wPxl+P), p-value=0.158. Grade 3/4 Adverse Events were 36% vs. 31% (p=0.624); the most frequent G3/4 toxicities were vomiting (5.8% saracatinib vs. 8.6% placebo), abdominal pain (5.8% vs. 0%) and diarrhoea (4.3% vs. 5.7%). Febrile neutropenia was more common in the saracatinib arm (4.3%) than placebo (0%). Response, PFS and OS were all significantly (p<0.05) better in patients with taxane interval ≥6 m/no prior taxane (n=85) than those <6 m (n=22), regardless of randomisation.<p></p> Conclusions: Saracatinib does not improve activity of weekly paclitaxel in platinum-resistant ovarian cancer. Taxane-free interval of ≥6 m/no prior taxane was associated with better outcome in both groups.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mcneish, Professor Iain
• Authors: McNeish, I.A., Ledermann, J. A., Webber, L., James, L., Kaye, S. B., Hall, M., Hall, G., Clamp, A., Earl, H., Banerjee, S., Kristeleit, R., Raja, F., Feeney, A., Lawrence, C., Dawson-Athey, L., Persic, M., and Khan, I.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Annals of Oncology
• Publisher: Oxford University Press
• ISSN: 0923-7534
• ISSN (Online): 1569-8041