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%)
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
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) Overall G3 or more = 50/140 (S + P); 24/80 (P) Anaemia = 13/140; 7/80 Neutropaenia = 9/140 (S + P); 8/80 (P) Fatigue = 11/140 (S + P); 4/80 (P) Hypokalaemia = 11/140 (S + P); 2/80 (P) Nausea = 5/140 (S + P); 3/80 (P) Vomiting = 2/140 (S + P); 3/80 (P) Abdominal pain = 10/140 (S + P); 4/80 (P) Diarrhoea = 2/140 (S + P); 3/80 (P) VTE = 8/140 (S + P); 6/80 (P) Dyspneoa = 6/140 (S + P); 2/80 (P)
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.