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

Publication date: Available online 4 November 2016
Source:European Journal of Cancer
Author(s): David Miles, David Cameron, Igor Bondarenko, Lyudmila Manzyuk, Juan Carlos Alcedo, Roberto Ivan Lopez, Seock-Ah Im, Jean-Luc Canon, Yaroslav Shparyk, Denise A. Yardley, Norikazu Masuda, Jungsil Ro, Neelima Denduluri, Stanislas Hubeaux, Cheng Quah, Carlos Bais, Joyce O'Shaughnessy
AimMERiDiAN evaluated plasma vascular endothelial growth factor-A (pVEGF-A) prospectively as a predictive biomarker for bevacizumab efficacy in metastatic breast cancer (mBC).MethodsIn this double-blind placebo-controlled randomised phase III trial, eligible patients had HER2-negative mBC previously untreated with chemotherapy. pVEGF-A was measured before randomisation to paclitaxel 90 mg/m² on days 1, 8 and 15 with either placebo or bevacizumab 10 mg/kg on days 1 and 15, repeated every 4 weeks until disease progression, unacceptable toxicity or consent withdrawal. Stratification factors were baseline pVEGF-A, prior adjuvant chemotherapy, hormone receptor status and geographic region. Co-primary end-points were investigator-assessed progression-free survival (PFS) in the intent-to-treat and pVEGF-Ahigh populations.ResultsOf 481 patients randomised (242 placebo–paclitaxel; 239 bevacizumab–paclitaxel), 471 received study treatment. The stratified PFS hazard ratio was 0.68 (99% confidence interval, 0.51–0.91; log-rank p = 0.0007) in the intent-to-treat population (median 8.8 months with placebo–paclitaxel versus 11.0 months with bevacizumab–paclitaxel) and 0.64 (96% confidence interval, 0.47–0.88; log-rank p = 0.0038) in the pVEGF-Ahigh subgroup. The PFS treatment-by-VEGF-A interaction p value (secondary end-point) was 0.4619. Bevacizumab was associated with increased incidences of bleeding (all grades: 45% versus 27% with placebo), neutropenia (all grades: 39% versus 29%; grade ≥3: 25% versus 13%) and hypertension (all grades: 31% versus 13%; grade ≥3: 11% versus 4%).ConclusionThe significant PFS improvement with bevacizumab is consistent with previous placebo-controlled first-line trials in mBC. Results do not support using baseline pVEGF-A to identify patients benefitting most from bevacizumab.Clinical trials registrationClinicalTrials.gov NCT01663727.



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