Randomised trial of paclitaxel in combination with platinum chemotherapy versus platinum-based chemotherapy in the treatment of relapsed ovarian cancer (ICON4 / OVAR 2.2)

Category: Gynecologic Cancer

Authors: J. A. Ledermann, on behalf of ICON and AGO Collaborators; Medical Research Council (MRC) Clinical Trials Unit, London, UK

Abstract:Patients (pts) with ovarian cancer relapsing ≥ 6 months after platinum therapy are generally retreated with platinum-based chemotherapy. ICON4 (co-ordinated by MRC and Mario Negri Institute (IRFMN)) and OVAR 2.2 (co-ordinated by Arbeitsgemeinschaft Gynaekologische Onkologie (AGO)) were two parallel randomised trials comparing a minimum of 6 cycles of platinum chemotherapy (Plat) versus paclitaxel plus Plat (Pac-Plat) in pts relapsing with a treatment-free interval of ≥ 6 months (MRC/AGO), or ≥ 12 months (IRFMN). Protocol doses were: 175mg/m² or 185mg/m², paclitaxel; minimum AUC of 5, carboplatin; 75 mg/m², cisplatin alone; 50mg/m², cisplatin in combination. ICON4/OVAR2.2 was a collaboration between groups in UK, Italy, Norway, Germany and Switzerland (SIAK); 802 patients were randomised between 01/96 and 03/02. Data were analysed as a single trial stratified by randomising group (MRC, IRFMN, AGO). Pt characteristics were similar both across the randomising groups and treatment arms. Median age was 60 and 8% pts had more than 1 previous line of chemotherapy. Last chemotherapies received were: carboplatin (34%), cisplatin (30%), and carboplatin plus taxane (36%). By 10/02, with a median follow-up of 34 months, 674 (84%) pts had progressed or died, with a hazard ratio (HR) of 0.77 in favour of Pac-Plat (p=0.006). This translates into an absolute improvement in 1-year progression-free survival (PFS) of 9% (from 40% to 49%; 95% confidence interval (CI) 4%-15%). 463 (58%) pts have died; HR ratio is 0.77 in favour of Pac-Plat (p=0.006), which translates into an absolute improvement in 2-year survival of 9% (from 50% to 59%; 95% CI 3%-14%). There was no evidence that the effect of Pac-Plat is larger or smaller in any subgroups (randomising group, time to relapse, number of previous lines of chemotherapy, type of prior chemotherapy, age and performance status). These results suggest that Pac-Plat improves survival and PFS in pts with platinum-sensitive relapsed ovarian cancer compared with Plat alone.