Pegylated liposomal doxorubicin and carboplatin (C-PLD) versus paclitaxel and carboplatin (C-P) in platinum-sensitive ovarian cancer (OC) patients (pts): Treatment at recurrence and overall survival (OS) final analysis from CALYPSO phase III GCIG trial.

Abstract

5052 Background: CALYPSO is a large international randomized phase III trial comparing C-PLD and C-P in pts with OC in late relapse. Results of the progression-free survival (PFS), the primary endpoint, suggest a benefit in pts treated with C-PLD with a hazard ratio (HR) of 0.82 (P =.005). Overall severe non-hematologic toxicity (36.8% v 28.4%; P < .01) - including alopecia, neurotoxicity and carboplatin hypersensitivity leading to early discontinuation (15% v 6%; P < .001) - occurred more frequently in the C-P arm. Methods: From 04/05 to 10/07, 976 eligible pts were randomized to either C-P (carboplatin AUC 5 iv d1 + paclitaxel [P] 175 mg/m2 3h iv d1, q3w) or C-PLD (Carboplatin + PLD 30 mg/m2 iv d1 q4w) for at least 6 cycles. It was explored whether the treatment effect on PFS recently observed in CALYPSO was maintained after further treatment. OS of pts was analysed. Results: Median follow-up is 40 months (mo). 832 pts (86%) have progressed after CALYPSO treatment (C-PLD or C-P). At time of first progression following CALYPSO, median platinum-free interval (C-PLD:5.2, C-P: 5.5 mo) and percentage of pts receiving platinum-based treatment (C-PLD: 27% , C-P: 26%) were similar in both arms. Pts initially treated with C-PLD had significantly less risk of 2nd treatment failure compared with those initially receiving C-P, with a HR of 0.83 (95% CI: 0.73,0.96, p=0.01). There was a significant imbalance in the cross-over rate of PLD and paclitaxel between both arms (from C-PLD to P: 34%, from C-P to PLD: 57%). Median OS of the global population (n=621 events) was 31.5 mo with a HR of 0.987 (P = 0.87) for C-PLD compared to C-P. Conclusions: In pts with OC in late relapse, the benefit in disease control of C-PLD over C-P was maintained at 1st treatment following CALYPSO relapse. OS was similar in both arms while cross-over treatment rate was superior in the C-P arm.