Pazopanib and fosbretabulin in recurrent ovarian cancer (PAZOFOS): A multi-centre, phase 1b and open-label, randomised phase 2 trial
Authors
Morgan, Robert DavidBanerjee, S
Hall, M
Clamp, Andrew R
Zhou, Cong
Hasan, Jurjees
Orbegoso, C
Taylor, Sarah
Tugwood, Jonathan D
Lyon, AR
Dive, Caroline
Rustin, GJS
Jayson, Gordon C
Affiliation
Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UKIssue Date
2020
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OBJECTIVE: Vascular co-option is a resistance mechanism to anti-angiogenic agents, but combinations of anti-vascular agents may overcome this resistance. We report a phase 1b and randomised phase 2 trial to determine the safety and efficacy of pazopanib with fosbretabulin. METHODS: Eligible patients had recurrent, epithelial ovarian cancer with a platinum-free interval (PFI) of 3 to 12 months. Patients were stratified according to PFI (>6 versus ?6 months) and prior bevacizumab use. RESULTS: Twelve patients were treated in the phase 1b. Commonest grade ? 2 adverse events (AEs) were hypertension (100%), neutropenia (50%), fatigue (50%), vomiting (50%). There was one DLT (grade 3 fatigue). The recommended phase 2 dose level was fosbretabulin 54 mg/m2 on days 1, 8 and 15 and pazopanib 600 mg once daily (od), every 28 days, which was then compared to pazopanib 800 mg od in a randomised phase 2 trial. Twenty-one patients were randomised (1:1) in the phase 2 trial. In phase 1b and phase 2, four patients treated with pazopanib and fosbretabulin developed reversible, treatment-related cardiac AEs, leading to premature discontinuation of the study. In the phase 2 trial, the median PFS was 7.6 months (95% CI 4.1-not estimated) versus 3.7 months (95% CI 1.0-8.1) in favour of the experimental arm (HR 0.30, 95% CI 0.09-1.03, P = .06). CONCLUSIONS: It remains unclear whether pazopanib with with fosbretabulin is an efficacious regimen to treat epithelial ovarian cancer. Effective cardiac risk mitigation is needed to increase the tolerability and maximize patient safety in future trials.Citation
Molloy K, Jonak C, Sherida F, Woei A, Guenova E, Busschots A, et al. An overall response in skin is associated with improved HRQoL in patients with MF/SS enrolled in the PROCLIPI study. European Journal of Cancer. 2019;119:S39.Journal
Gynecologic OncologyDOI
10.1016/j.ygyno.2020.01.005PubMed ID
31932108Additional Links
https://dx.doi.org/10.1016/j.ygyno.2020.01.005Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1016/j.ygyno.2020.01.005