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PVEGF-A not predictive of bevacizumab benefit in HER-2–negative metastatic breast cancer
Baseline plasma vascular endothelial growth factor-A levels did not predict whether patients with HER-2–negative metastatic breast cancer would benefit from treatment with bevacizumab, according to results of randomized, phase 3 trial.
“In three randomized phase 3 trials, adding bevacizumab to first-line chemotherapy for HER-2–negative metastatic breast cancer significantly improved PFS and overall response rate, but not OS,” David Miles, MB, BS, BSc, FRCP, MD, professor and medical oncologist at Mount Vernon Cancer Centre in London, and colleagues wrote. “Initial analyses in lung, colorectal and renal cancers identified a prognostic but not predictive effect of plasma vascular endothelial growth factor-A (pVEGF-A). However, retrospective analyses of phase 3 trials in HER-2–negative metastatic breast cancer, gastric and pancreatic cancers using a novel immunologic multiparameter chip technology enzyme-linked immunosorbent assay suggested potential predictive and prognostic effects of pretreatment pVEGF-A in bevacizumab-treated patients.”
The double blind, placebo-controlled MERiDiAN trial included 481 patients with HER-2–negative metastatic breast cancer who had not previously received chemotherapy.
Miles and colleagues randomly assigned patients to a 90-mg/m2 dose of paclitaxel with either placebo (n = 242) or 10 mg/kg bevacizumab (n = 239) on days 1, 8 and 15 every 4 weeks. Treatment continued until unacceptable toxicity, consent withdrawal or disease progression.
Miles and colleagues measured pVEGF-A at baseline.
PFS in the group with high pVEGF-A and the intent-to-treat populations served as the primary endpoint.
In the intent-to-treat population, patients assigned bevacizumab plus paclitaxel achieved longer median PFS (11 months vs. 8.8 months; HR = 0.68; 99% CI, 0.51-0.91).
In the group with high pVEGF-A levels, researchers observed longer median PFS among bevacizumab-treated patients (9.6 months vs. 7.3 months; HR = 0.64; 96% CI, 0.47-0.88). However, the VEGF-A-by-treatment interaction test for PFS in the intention-to-treat population did not support a predictive effect of pVEGF-A, the researchers wrote.
Bevacizumab-treated patients experienced higher rates of hypertension (all grades, 31% vs. 13%), neutropenia (all grades, 39% vs. 29%; grade ≥ 3, 25% vs. 13%) and bleeding (all grades, 45% vs. 27%).
“The significant PFS benefit from adding bevacizumab to paclitaxel is consistent with previous first-line placebo-controlled trials of bevacizumab in metastatic breast cancer,” Miles and colleagues wrote. “MERiDiAN results did not support baseline pVEGF-A as a predictive marker for bevacizumab PFS benefit. Based on these findings and previous retrospective analyses, pVEGF-A does not appear to identify patients deriving the most substantial benefit from bevacizumab. In the overall MERiDiAN population, median PFS with bevacizumab–paclitaxel replicates that in three previous randomized phase 3 trials evaluating this combination.” – by Andy Polhamus
Disclosure: Miles reports a consultant or advisory role with Roche/Genentech. Please see the full study for a list of all other researchers’ relevant financial disclosures.