A randomized phase III trial in patients with recurrent platinum sensitive ovarian cancer comparing efficacy and safety of paclitaxel micellar and Cremophor EL-paclitaxel.

OBJECTIVE: Paclitaxel micellar was developed to avoid Cremophor-EL (Cr-EL) associated dose limiting toxicity and to allow a shorter infusion time. The efficacy and safety of paclitaxel micellar (+carboplatin) was compared to Cr-EL paclitaxel (+carboplatin) in recurrent platinum-sensitive ovarian, fallopian tube or peritoneal carcinoma. METHODS: This was a multicentre, open-label, randomized phase III trial. Adult patients with recurrent disease was assigned to six 3-week cycles of paclitaxel micellar (250 mg/m2) administered as 1-h infusion or Cr-EL paclitaxel (175 mg/m2) as 3-h infusion. Both arms received carboplatin (AUC 5-6). Primary objective was non-inferiority for progression free survival (PFS) using computed tomography scans. Overall survival (OS) was included as secondary endpoint. RESULTS: Between 2009 and 2013, 789 patients were randomized to receive experimental (N = 397) or control (N = 392) treatment. PFS for paclitaxel micellar was non-inferior to Cr-EL paclitaxel with a hazard ratio of 0.86 (95% CI: 0.72;1.03) in the per protocol population (PP), favouring paclitaxel micellar (non-inferiority margin was 1.2). Non-inferiority of OS was shown in the PP population with a hazard ratio of 0.95 (95% CI: 0.78; 1.16), favouring paclitaxel micellar (non-inferiority margin was 1.185). The most common adverse event was neutropenia (grade ≥ 3); 245 patients (79%) for paclitaxel micellar vs 213 patients (66%) for Cr-EL paclitaxel. The frequency of peripheral sensory neuropathy (any grade) was similar between the arms; 16% for paclitaxel micellar and 20% for Cr-EL paclitaxel. CONCLUSION: Paclitaxel micellar (+ carboplatin) is non-inferior to Cr-EL paclitaxel (+ carboplatin) in terms of PFS and OS in the studied population. It provides a treatment option of a higher paclitaxel dose with a shorter infusion time without mandatory premedication. TRIAL REGISTRATION NUMBER: 2008-002668-32 (EudraCT), NCT00989131 (ClinicalTrials.gov).

Health-related quality of life in women with recurrent ovarian cancer receiving paclitaxel plus trebananib or placebo (TRINOVA-1).

BACKGROUND: To evaluate the influence of treatment on health-related quality of life (HRQoL) in 919 women with recurrent ovarian cancer enrolled in the TRINOVA-1 study, a randomized, placebo-controlled phase III study that demonstrated that trebananib 15 mg/kg QW plus weekly paclitaxel significantly improved progression-free survival (PFS) compared with placebo plus weekly paclitaxel (7.2 versus 5.4 months; hazard ratio, 0.66; 95% confidence interval 0.57-0.77; P < 0.001). PATIENTS AND METHODS: HRQoL was assessed with the Functional Assessment of Cancer Therapy-Ovary [FACT-O; comprising FACT-G and the ovarian cancer-specific subscale (OCS)] and EuroQOL EQ-5D instruments before treatment on day 1 of weeks 1, 5, 9, 13, 17, and every 8 weeks thereafter and at the safety follow-up visit. A pattern-mixture model was used to evaluate the influence of patient dropout on FACT-O and OCS scores over time. RESULTS: Of 919 randomized patients, 834 (91%) had a baseline and ≥1 post-baseline HRQoL assessment. At baseline, scores for all instruments were similar for both arms. At 25 weeks, mean ± SD changes from baseline were negligible, with mean ± SD changes typically <1 unit from baseline: -2.4 ± 16.6 in the trebananib arm and -1.6 ± 15.2 in the placebo arm for FACT-O, -0.71 ± 5.5 in the trebananib arm and -0.86 ± 4.9 in the placebo arm for OCS, and -0.02 ± 0.22 in the trebananib arm and 0.02 ± 0.19 in the placebo arm for EQ-5D. Distribution of scores was similar between treatment arms at baseline and over the course of the study. In pattern-mixture models, there was no evidence that patient dropout affected differences in mean FACT-O or OCS scores. Edema had limited effect on either FACT-O or OCS scores in patients with grade ≥2 edema or those with grade 1 or no edema. CONCLUSIONS: Our results demonstrate that the improvement in PFS among patients in the trebananib arm in the TRINOVA-1 study was achieved without compromising HRQoL. CLINICALTRIALSGOV IDENTIFIER: NCT01204749.