Cediranib Plus Carboplatin–Paclitaxel Tested For Advanced Cervical Cancer

A vascular endothelial growth factor receptor 1, 2 and 3 inhibitor, in combination with chemotherapy, shows efficacy in patients with advanced cervical cancer

medwireNews: CIRCCa trial results suggest that cediranib, given alongside carboplatin plus paclitaxel, may have significant efficacy in women with metastatic or recurrent cervical cancer.

The 34 patients randomly assigned to receive the vascular endothelial growth factor receptor (VEGFR) 1, 2 and 3 tyrosine kinase inhibitor alongside chemotherapy had significantly longer progression-free survival (PFS) than the 35 patients given placebo, at a median of 8.1 versus 6.7 months.

The researchers say the phase II trial was underpowered to detect a difference in overall survival between the treatment groups and further hampered by early closure due to drug access.

Nevertheless, lead author R Paul Symonds, from the University of Leicester in the UK, and team also report a significant decrease in plasma levels of soluble (s)VEGFR2 between baseline and day 28 of treatment in the cediranib group, whereas patients given placebo showed an increase.

“The reductions in sVEGFR2 concentration recorded in our trial are consistent with the findings from other cancers and support its use as a biomarker of the biological activity of cediranib”, they write in The Lancet Oncology.

However, cediranib-treated patients, followed up for a median of 24.2 months, had a higher rate of grade 3 or more severe events than controls, including diarrhoea (16 vs 3%), fatigue (13 vs 6%), leukopenia (16 vs 9%), neutropenia (31 vs 11%) and febrile neutropenia (16 vs 0%). Cediranib was also associated with an increased risk of grade 2 or 3 hypertension, at 34% versus 11% in controls.

The cediranib and control treatment arms had a similar rate of severe adverse events, affecting 19 versus 18 patients.

“The GOG study using a monoclonal antibody to VEGF and our trial of a VEGFR tyrosine kinase inhibitor shows the value of targeting angiogenesis in combination with chemotherapy in the management of metastatic or relapsed cervical cancer”, the researchers write.

They continue: “In view of the impressive overall survival advantage shown in GOG 240, the value of a direct comparison between bevacizumab and cediranib is debatable, but the evidence that both agents are effective opens up the potential for studies of multi-anti-angiogenic combinations, sequencing of anti-angiogenics, or trials of anti-angiogenics and biological agents with pre-existing evidence of synergy, including poly-ADP ribose polymerase inhibitors.”

Reference

Symonds RP, Gourley C, Davidson S, et al. Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer (CIRCCa): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Oncol 2015; Advance online publication 13 October. DOI: http://dx.doi.org/10.1016/S1470-2045(15)00220-X

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