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RESEARCH PRODUCT

Final results of OV16, a phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel (CP) versus CP in first-line chemotherapy for advanced epithelial ovarian cancer (EOC): A GCIG study of NCIC CTG, EORTC-GCG, and GEICO.

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5502 Background: Topotecan was evaluated in a novel combination regimen in comparison to standard therapy in front-line EOC. Methods: Women with newly diagnosed advanced EOC stages IIB-IV, ECOG performance status (PS) 0-1, age < 75, were randomized to either Arm 1: cycles 1 - 4: cisplatin 50 mg/m2 d1 plus topotecan 0.75 mg/m2 d1-5 IV; cycles 5 - 8: paclitaxel 175 mg/m2over 3 hrs d1 followed by carboplatin AUC5 day 1 or Arm 2: paclitaxel plus carboplatin as in Arm 1 for 8 cycles. The primary endpoint was progression free survival (PFS) and secondary endpoints included objective response, overall survival (OS), adverse event (AE) and Quality of Life (QoL). The sample size required 800 pts and 631 events to detect an improvement in PFS from 16 to 20 months (power 80%, 2-sided alpha 0.05). Results with 3.6 years median follow-up (MFU) were reported previously: there was no significant difference in PFS (Hoskins P, JNCI 2010). Final results including OS after MFU of 8.2 years are reported. Results: From 2001 to 2005, 819 pts (409 Arm 1, 410 Arm 2) were randomized. 704 PFS events and 605 deaths have occurred. PFS results are similar to first report: Median (months [mo]): 14.6 (Arm 1) and 16.2 (Arm 2), hazard ratio (HR) 1.03 (95% CI:0.81-1.30; p = 0.83). Median OS is 44.2 mo (Arm 1) and 44.8 mo (Arm 2), HR: 0.92 (95% CI:0.71-1.19; p=0.54). Baseline factors found to be independent predictors of OS in multivariate analysis are: a) pre-randomization surgery (debulking with no macro residual disease (MRD) to no debulking HR: 0.47; 95%CI:0.37-0.58; p < 0.0001; debulking with MRD (<1 cm) to no debulking HR: 0.76; 95%CI:0.61-0.94; p = 0.01), b) Stage (stage II to III or IV HR:0.52; 95%CI:0.36-0.76; p = 0.0007) and c) PS (0 vs 1 HR:0.76; 95%CI:0.63-0.91; p = 0.004). Post-treatment AEs were not significantly different in the two arms. Conclusions: OV16 final results confirm that sequential doublets of topotecan and cisplatin followed by carboplatin and paclitaxel offer no improvement in outcomes compared to carboplatin and paclitaxel. Pretreatment debulking, stage II and PS 0 are predictive of longer OS. Clinical trial information: NCT00028743.