Cediranib Extends PFS In Recurrent Platinum-Sensitive Ovarian Cancer Patients

ICON6 results support the administration of cediranib alongside chemotherapy and as subsequent maintenance therapy in ovarian cancer patients who relapse after first-line chemotherapy

medwireNews: Concurrent administration of cediranib with platinum-based chemotherapy followed by cediranib maintenance significantly prolongs progression-free survival (PFS) in women with relapsed platinum-sensitive ovarian cancer, phase III findings indicate.

Jonathan Ledermann, from University College London Cancer Institute in the UK, and fellow ICON6 investigators say that “the results of cediranib and bevacizumab trials show that antiangiogenic treatment is a new treatment option for women with relapsed ovarian cancer, and cediranib is the first oral drug to be beneficial in this setting.”

However, in a piece accompanying the trial in The Lancet, the commentator points out that the data are “less convincing” than they would have been if the trial design had not undergone “a major revision” following the drug company’s decision to cease cediranib development due to negative overall survival results in three pivotal trials of other malignancies.

John Norrie, from the University of Aberdeen in the UK, notes that instead of a sample size of 2000, the trial ultimately included 456 participants and the primary outcome was changed from overall survival to PFS.

Nonetheless, he congratulates the researchers, the independent Data Monitoring Committee and the funders “on having the vision and creativity to redesign the study, within the constraints of the remaining drug available.”

In the double-blind trial, ovarian cancer patients with disease recurrence after first-line chemotherapy were randomly assigned to receive platinum-based chemotherapy either alongside placebo and followed by maintenance placebo (arm A), alongside once-daily cediranib and followed by maintenance placebo (arm B), or together with once-daily cediranib and followed by maintenance cediranib (arm C).

Over a median follow-up of 19.5 months, median PFS was 11.0 months for the 164 patients who received cediranib in both phases compared with 8.7 months for the 118 women given placebo in both phases, with a significant hazard ratio of 0.56.

The difference between the groups remained statistically significant when arm B, in which PFS was a median of 9.9 months for 174 participants, was included in the analysis, with the “greatest benefit” derived from the use of cediranib in both phases, say the researchers.

They add that the Kaplan–Meier plots suggest that in arm B “the early benefit of addition of cediranib to chemotherapy seemed to dissipate as patients switched to placebo maintenance.”

Although overall survival data are not yet mature, Jonathan Ledermann et al write that ICON6 is the first trial to show the benefit of a vascular endothelial growth factor receptor 1–3 tyrosine kinase inhibitor in this patient population.

However, the benefit came at the cost of toxic effects, with 39% of patients in arm C and 27% in arm B discontinuing the trial drug as a result of adverse effects, compared with 12% in arm A.

Diarrhoea and voice changes of any grade were more common with cediranib than placebo during both the chemotherapy and maintenance phases, while hypertension and hypothyroidism occurred more often with cediranib during the chemotherapy and maintenance phases, respectively.

References

Ledermann JA, Embleton AC, Raja F, et al. Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2016; 387: 1066–1074. doi: http://dx.doi.org/10.1016/S0140-6736(15)01167-8

Norrie J. ICON-6: the danger of changing study design midstream. Lancet 2016; 387: 1031–1032. doi: http://dx.doi.org/10.1016/S0140-6736(16)00658-9

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016