VEGF-A Levels Fail To Predict Bevacizumab Response In Metastatic HER2-Negative Breast Cancer

High circulating levels of vascular endothelial growth factor A do not correlate with bevacizumab efficacy in metastatic HER2-negative breast cancer

medwireNews: MERiDiAN trial results have failed to confirm plasma vascular endothelial growth factor (pVEGF)-A as a predictive biomarker for bevacizumab efficacy in metastatic, HER2-negative breast cancer.

The phase III study did add further evidence in support of the anti-VEGF-A agent as a treatment for treatment-naive metastatic disease in HER2-negative patients, however, with significant improvement in progression-free survival (PFS) for those given bevacizumab plus paclitaxel versus patients treated with paclitaxel plus placebo.

“In the overall MERiDiAN population, median PFS with bevacizumab–paclitaxel replicates that in three previous randomised phase III trials evaluating this combination”, the authors write in the European Journal of Cancer.

Investigator-assessed PFS was a median of 11.0 months for the 239 patients randomly assigned to receive paclitaxel 90 mg/m2 on days 1, 8 and 15 of a 4-week cycle plus bevacizumab 10 mg/kg on days 1 and 15 versus 8.8 months for the 242 patients given paclitaxel plus placebo, giving a significant hazard ratio (HR) of 0.68.

Patients’ baseline pVEGF-A concentration was classified as high if measured at 5.05 pg/mL or above, explain David Miles, from Mount Vernon Cancer Centre in London, UK, and co-workers.

Median investigator-assessed PFS in patients with a high pVEGF-A concentration also significantly differed between those given paclitaxel plus bevacizumab and those given paclitaxel plus placebo, at 9.6 versus 7.3 months and an HR of 0.64.

But the secondary endpoint of PFS VEGF-A-by-treatment interaction did not reach statistical significance, the authors emphasize.

“Given the complexity and multifactorial nature of the underlying angiogenic mechanisms, it is perhaps unrealistic to expect a single biomarker to predict benefit from anti-VEGF therapy”, they say.

David Miles et al continue: “Despite an extensive search for a biomarker for bevacizumab efficacy and mandatory biomarker sampling in MERiDiAN, there is no evidence suggesting that factors other than clinical reasons should influence patient selection for bevacizumab.”

Bleeding of any grade was more common with bevacizumab than placebo (44.5 vs 26.6%), as were neutropenia and associated complications (38.7 vs 29.2%), including a higher rate of grade 3 or more severe events (24.8 vs 12.9%).

All-grade and grade 3 or above hypertension was also more common with bevacizumab (31.1 vs 13.3% and 10.9 vs 4.3%, respectively), and although venous thromboembolic events were overall comparable, grade 3 or more severe events were more common in bevacizumab-treated patients (3.8 vs 1.3%), driven by seven cases of pulmonary embolism.

Reference

Miles D, Cameron D, Bondarenko I, et al. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. Eur J Cancer; Advance online publication 4 November 2016. doi: http://dx.doi.org/10.1016/j.ejca.2016.09.024

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