Lui 2016.
Methods | Multi‐centre open‐label phase II randomised controlled trial | |
Participants | 223 women with advanced or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer that was platinum resistant or refractory per Gynecologic Oncology Group criteria. Participants underwent mandatory pretreatment core needle biopsy and submitted archived tumour samples as available. Age Seribantumab + Paclitaxel (S + P) 58.5 years (30 to 82); Paclitaxel (P) = 60.6 years (28 to 85) Histology Seribantumab + Paclitaxel (S + P): serous = 103 (73.6); endometrioid = 7 (5.0%); clear cell = 6 (4.3%); transitional cell = 2 (1.4%); mixed epithelial = 0 (0%); undifferentiated = 7 (5.0%); other = 12 (8.6%) Paclitaxel (P): serous = 55 (66.2%); endometrioid = 5 (6.0%); clear cell = 2 (2.4%); transitional cell = 0 (0%); mixed epithelial = 1 (1.2%); undifferentiated = 0 (0%); other = 18 (21.7%) Number of platinum‐based therapies S + P = 1 cycle = 25 (17.9%); 2 or more = 114 (81.4%) P = 1 cycle = 17 (20.5%); 2 or more = 65 (78.3%) |
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Interventions | Seribantumab + Paclitaxel (S + P) vs Paclitaxel (P) Seribantumab = 40 mg/kg loading dose, then 20 mg/kg once per week Paclitaxel = 80 mg/m² during cycle 1, with optional modification in subsequent cycles to 80 mg/m² once per week for 3 weeks followed by 1 week of rest |
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Outcomes | 260 participants enrolled; 223 eligible S + P = 140 participants; P = 83 participants OS Median OS = S + P = 13.7 months; P = 10.12 months (HR 0.991, 95% CI 0.62 to 1.584; P = 0.972) PFS Median PFS = S + P = 3.75 months vs P = 3.68 months (HR 1.027, 95% CI 0.741 to 1.425; P = 0.864) QoL "no significant changes from baseline"; data not provided Overall response rate S + P 13.6% (95% CI 19.9 to 19.6%) (n = 140) P = 18.1% (95% CI 9.8 to 26.4%) (n = 83) Toxicity (G3 or more)
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Notes | Trial was supported by Merrimack Pharmaceuticals, and several trial authors were employees of the company. | |
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Unclear risk | No details about methods for randomisation provided in the paper |
Allocation concealment (selection bias) | Unclear risk | No details about methods for allocation concealment provided in the paper |
Blinding of participants and personnel (performance bias) Objective outcome measures (Overall Survival) | Low risk | Unlikely to be affected by lack of blinding |
Blinding of participants and personnel (performance bias) Subjective outcome measures (PFS; Toxicity; QoL) | High risk | Open‐label |
Blinding of outcome assessment (detection bias) Objective outcome measures (overall survival) | Unclear risk | Unlikely to be affected by lack of blinding |
Blinding of outcome assessment (detection bias) Subjective outcome measures (PFS, Toxicity, QoL) | High risk | Open‐label |
Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Intention‐to‐treat analysis was undertaken, and all participants were accounted for in the CONSORT diagram and for PFS and OS on the basis of ITT, but reasons for withdrawal from toxicity outcomes for 3 participants are not clear. |
Selective reporting (reporting bias) | Unclear risk | All expected outcomes reported, although specific data for QoL not reported |
Other bias | Unclear risk | Several trial authors are employees of the drug company supporting the trial, although no significant effect can be seen. |