CRC Outcomes Comparable For Tivozanib And Bevacizumab Regimens

Tivozanib-based chemotherapy is not superior to a bevacizumab-based regimen for metastatic colorectal cancer

medwireNews: The selective vascular endothelial growth factor receptor (VEGFR)-1, -2 and -3 inhibitor tivozanib plus modified (m)FOLFOX6 does not improve the outcomes of patients with metastatic colorectal cancer (CRC) over that achieved by bevacizumab plus mFOLFOX6, study findings indicate.

The phase II BATON-CRC trial was halted after a prespecified interim futility analysis indicated that the tivozanib plus mFOLFOX6 regimen did not offer superior progression-free survival (PFS) to the bevacizumab regimen, at a median of 9.4 versus 10.7 months.

The 177 patients randomly assigned to receive tivozanib plus mFOLFOX6 and the 88 patients given the bevacizumab combination also achieved a comparable overall rate of response (45.2 vs 43.2%) and complete response (2.3 vs 1.1%). The two patient groups also had a similar duration of response (7.4 vs 9.3 months) and time to treatment failure (5.5 vs 5.4 months).

However, post hoc analysis looking at potential biomarkers for response to tivozanib and bevacizumab indicated that PFS tended to be longer in patients with VEGFR-2 coreceptor neuropilin-1 (NRP-1) levels below the median than those with higher concentrations.

And this PFS difference reached significance in low NRP-1 patients treated with tivozanib, at 17.9 versus 11.2 months for those given bevacizumab, with a hazard ratio of 0.38.

By contrast, PFS was comparable in patients with high NRP-1 levels given the tivozanib and bevacizumab regimens, say Al Benson III, from Northwestern University in Chicago, Illinois, USA, and co-investigators.

The team notes that the safety profiles were comparable for the two treatment arms and similar to that reported previously for tivozanib.

Diarrhoea was the most common all-grade treatment-emergent side effect, affecting 58.2% of the tivozanib- and 57.5% of bevacizumab-treated patients, while neutropenia was the most common grade 3 or 4 treatment-emergent event, at 39.5% and 24.1%.

Adverse events led to discontinuation in 41.2% of the tivozanib group and 34.5% of the bevacizumab group, most commonly associated with pulmonary embolism and deep vein thrombosis, respectively. Serious adverse events occurred in 46.3% and 48.3% of the treatment arms, respectively.

“On the basis of the results, further study of tivozanib is not warranted in an unselected population”, the authors recommend in Clinical Cancer Research.

However, noting that that low NRP-1 may be a potential biomarker for predicting tivozanib activity, they conclude: “Although these results require further validation, they may warrant further study to determine whether tivozanib may be a potential oncology treatment in selected patient populations.”

Reference

Benson AB 3rd, Kiss I, Bridgewater J, et al. BATON-CRC: A phase II randomized trial comparing tivozanib plus mFOLFOX6 with bevacizumab plus mFOLFOX6 in stage IV metastatic colorectal cancer. Clin Cancer Res 2016; Advance online publication 2 September. DOI: 10.1158/1078-0432.CCR-15-3117

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