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

I. A. McNeish, J. A. Ledermann, L. Webber, L. James, S. B. Kaye, M. Hall, G. Hall, A. Clamp, H. Earl, S. Banerjee, R. Kristeleit, F. Raja, A. Feeney, C. Lawrence, L. Dawson-Athey, M. Persic, I. Khan

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

BACKGROUND: We investigated whether the Src inhibitor saracatinib (AZD0530) improved efficacy of weekly paclitaxel in platinum-resistant ovarian cancer.

PATIENTS AND METHODS: Patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer were randomised 2 : 1 to receive 8-week cycles of weekly paclitaxel (wPxl; 80 mg/m(2)/week ×6 with 2-week break) plus saracatinib (S; 175 mg o.d.) or placebo (P) continuously, starting 1 week before wPxl, until disease progression. Patients were stratified by taxane-free interval (<6 versus ≥6 months/no prior taxane). The primary end point was progression-free survival (PFS) rate at 6 months. Secondary end points included overall survival (OS) and response rate (RR).

RESULTS: A total of 107 patients, median age 63 years, were randomised. Forty-three (40%) had received >2 lines of prior chemotherapy. The 6-month PFS rate was 29% (wPxl + S) versus 34% (wPxl + P) (P = 0.582). Median PFS was 4.7 versus 5.3 months (hazard ratio 1.00, 95% confidence interval 0.65-1.54; P = 0.99). RR (complete + partial) was 29% (wPxl + S) versus 43% (wPxl + P), P value = 0.158. Grade 3/4 adverse events were 36% versus 31% (P = 0.624); the most frequent G3/4 toxicities were vomiting (5.8% saracatinib versus 8.6% placebo), abdominal pain (5.8% versus 0%) and diarrhoea (4.3% versus 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 months/no prior taxane (n = 85) than those <6 months (n = 22), regardless of randomisation.

CONCLUSIONS: Saracatinib does not improve activity of weekly paclitaxel in platinum-resistant ovarian cancer. Taxane-free interval of ≥6 months/no prior taxane was associated with better outcome in both groups.

TRIALS REGISTRATION: Clinicaltrials.gov NCT01196741; ISRCTN 32163062.

Original languageEnglish
Pages (from-to)1988-1995
Number of pages8
JournalAnnals of oncology : official journal of the European Society for Medical Oncology / ESMO
Volume25
Issue number10
DOIs
Publication statusPublished - 1 Oct 2014

Keywords

  • ovarian cancer
  • platinum-resistant
  • Src
  • taxane-free-interval
  • weekly paclitaxel

Fingerprint

Dive into the research topics of 'A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†'. Together they form a unique fingerprint.

Cite this