title: A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†.
abstract: BACKGROUND
  We investigated whether the Src inhibitor saracatinib (AZD0530) improved efficacy of weekly paclitaxel in platinum-resistant ovarian cancer.
  
  
  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.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01196741; ISRCTN 32163062.
authors: Institute of Cancer Sciences, University of Glasgow, Glasgow; Department of Medical Oncology, St Bartholomew's Hospital, London. Electronic address: iain.mcneish@glasgow.ac.uk.
authors: I A
authors: IA
authors: McNeish
authors: CR UK and UCL Cancer Trials Centre, University College London, London.
authors: J A
authors: JA
authors: Ledermann
authors: CR UK and UCL Cancer Trials Centre, University College London, London.
authors: L
authors: L
authors: Webber
authors: CR UK and UCL Cancer Trials Centre, University College London, London.
authors: L
authors: L
authors: James
authors: Department of Medical Oncology, Royal Marsden Hospital, Sutton.
authors: S B
authors: SB
authors: Kaye
authors: Division of Cancer Services, Mount Vernon Hospital, Northwood.
authors: M
authors: M
authors: Hall
authors: Leeds Cancer Centre, St James's University Hospital, Leeds.
authors: G
authors: G
authors: Hall
authors: Department of Medical Oncology, The Christie Hospital, Manchester.
authors: A
authors: A
authors: Clamp
authors: Department of Oncology, Addenbrooke's Hospital, Cambridge.
authors: H
authors: H
authors: Earl
authors: Department of Medical Oncology, Royal Marsden Hospital, Sutton.
authors: S
authors: S
authors: Banerjee
authors: Department of Medical Oncology, University College Hospital, London.
authors: R
authors: R
authors: Kristeleit
authors: CR UK and UCL Cancer Trials Centre, University College London, London.
authors: F
authors: F
authors: Raja
authors: CR UK and UCL Cancer Trials Centre, University College London, London.
authors: A
authors: A
authors: Feeney
authors: Department of Medical Oncology, St Bartholomew's Hospital, London.
authors: C
authors: C
authors: Lawrence
authors: Department of Medical Oncology, St Bartholomew's Hospital, London.
authors: L
authors: L
authors: Dawson-Athey
authors: Department of Oncology, Queen's Hospital, Burton upon Trent, UK.
authors: M
authors: M
authors: Persic
authors: CR UK and UCL Cancer Trials Centre, University College London, London.
authors: I
authors: I
authors: Khan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D052117:Benzodioxoles / Q000008:administration & dosage*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage*; D010984:Platinum / Q000009:adverse effects / Q000627:therapeutic use; D011799:Quinazolines / Q000008:administration & dosage*; D012186:Retroperitoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D052117:Benzodioxoles; D011799:Quinazolines; D010984:Platinum; C515233:saracatinib; D017239:Paclitaxel
keywords: Src; ovarian cancer; platinum-resistant; taxane-free-interval; weekly paclitaxel