A randomised placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer
Mené sur 107 patientes atteintes d'un cancer de l'ovaire, de la trompe de Fallope ou du péritoine résistant aux sels de platines (âge médian : 63 ans), cet essai randomisé évalue l'efficacité, du point de vue du taux de survie sans progression à 6 mois, et la toxicité de l'ajout de saracatinib au paclitaxel
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/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). 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.
Annals of Oncology 2014