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

Annals of oncology : official journal of the European Society for Medical Oncology / ESMO

PubMedID: 25070546

McNeish IA, Ledermann JA, Webber L, James L, Kaye SB, Hall M, Hall G, Clamp A, Earl H, Banerjee S, Kristeleit R, Raja F, Feeney A, Lawrence C, Dawson-Athey L, Persic M, Khan I. A randomised placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer. Ann Oncol. 2014;.
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 eight-week cycles of weekly paclitaxel (wPxl; 80 mg/m(2)/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).

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.

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.