Multicenter randomized phase III trial of 3-weekly paclitaxel/platinum (PC3w) versus weekly paclitaxel/platinum (PCw) induction therapy followed by PC3w maintenance therapy in advanced epithelial ovarian cancer (EOC)

Abstract

5538 Background: Response rates (RR) up to 50% were found with PCw in platinum resistant EOC. We compared the efficacy of first-line PCw induction therapy to PC3w. Methods: 270 patients (pts) with FIGO stage II-IV, Performance status (PS) 0–2 were randomly assigned to 3 x PC3w (P 175mg/m2 with either cisplatin [Cis] 75mg/m2 or carboplatin [Car] AUC 6) or 6 x PCw (P 90mg/m2 with either Cis 70mg/m2 or Car AUC 4, day 1,8,15 and day 29,36,43) followed by up to 6 cycles PC3w in both arms. Pts were stratified for FIGO stage, PS, tumor size and center. Primary endpoints were progression free survival (PFS) and overall survival (OS). Secondary endpoints were RR and toxicity. A total of 225 events were needed to detect a 10–13% absolute difference in PFS/OS with a power of 84% (one-sided). Results: 267 pts (134 TC-3w and 133 TCw) were eligible (3 pts wrong tumor type). Pt characteristics were well balanced; median age 58 years, serous 62%, residual disease >1cm 66%, FIGO stage II 7%, III 64%, IV 29%. Median dose-intensity for PC3w was: P 58(47–58) and Cis 25(22.5–25) mg/m2/w, Car 2(1.6–2) AUC/w, for PCw: P 60(36–60) and Cis 44.7(30–44.7) mg/m2/w and for Car 2.7(1,6–2,7) AUC/w. After a median follow-up of 39 months (m) (range 0.03 - 93.3m) 206 pts (77%) had progressed and 164 pts (61%) had died. Median PFS was 18m for TC3w and 19m for TCw, 5-year PFS was 20% and 18%, respectively (logrank test: p = 0.63). Median OS was 44m for TC3w and 45m for TCw, 5-year OS was 36% and 37%, respectively (logrank test: p = 0.87). RR after induction therapy in 176 pts with measurable disease was 72% for TC3w and 74% for TCw (p = 0.68). TCw was well tolerated. Grade 3/4 toxicity for TC3w vs. TCw was respectively, platelets 1.75% vs.1.55% (ns), WBC 5.5% vs. 8.7 (p = <0.0001), granulocytes 16.7% vs. 11.7% (p = <0.001) and delay 3% vs. 9% of the cycles. TCw induced less grade 2/3 muscular and joint pain (TC3w 6.3% and 3.5% vs. TCw 0.3% and 0.8% of the cycles) and less neurotoxicity (TC3w 6% vs. 1.6% of the pts in TCw). The other toxicities were similar in frequency and severity in both arms. Conclusions: TCw was well tolerated and had less granulocytopenia, neurotoxicity, and muscular and joint pain but did not yield benefit in terms of OS, PFS or RR. No significant financial relationships to disclose.