Miles, David and Cameron, David and Bondarenko, Igor and Manzyuk, Lyudmila and Alcedo, Juan Carlos and Lopez, Roberto Ivan and Im, Seock-Ah and Canon, Jean-Luc and Shparyk, Yaroslav and Yardley, Denise A and Masuda, Norikazu and Ro, Jungsil and Denduluri, Neelima and Hubeaux, Stanislas and Quah, Cheng and Bais, Carlos and O'Shaughnessy, Joyce (2017) 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. European journal of cancer, 70. pp. 146-155. ISSN 1879-0852
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Abstract
Aim: MERiDiAN evaluated plasma vascular endothelial growth factor-A (pVEGF-A) prospectively as a predictive biomarker for bevacizumab efficacy in metastatic breast cancer (mBC). Methods: In 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 endpoints were investigator-assessed progression-free survival (PFS) in the intent-to-treat and pVEGF-Ahigh populations. Results: Of 481 patients randomised (242 placeboepaclitaxel; 239 bevacizumabepaclitaxel), 471 received study treatment. The stratified PFS hazard ratio was 0.68 (99% confidence interval, 0.51e0.91; log-rank p Z 0.0007) in the intent-to-treat population (median 8.8 months with placeboepaclitaxel versus 11.0 months with bevacizumabepaclitaxel) and 0.64 (96% con-fidence interval, 0.47e0.88; log-rank p Z 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%). Conclusion: The 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 registration: ClinicalTrials.gov NCT01663727.
| Item Type: | Article |
|---|---|
| Additional Information: | DOI: http://dx.doi.org/10.1016/j.ejca.2016.09.024 DOI of original article: http://dx.doi.org/10.1016/j.ejca.2016.11.002. http://dx.doi.org/10.1016/j.ejca.2016.09.024 0959-8049/ª 2016 Published by Elsevier Ltd. |
| Uncontrolled Keywords: | Bevacizumab, Metastatic breast cancer, Predictive, Biomarker, Double-blind, VEGF-A, Weekly paclitaxel, Prospective |
| Subjects: | Oncology Biological Chemistry Genetics |
| Divisions: | Departments > Department of Oncology and Medical Radiology |
| Depositing User: | Елена Шрамко |
| Date Deposited: | 11 Sep 2017 11:15 |
| Last Modified: | 11 Sep 2017 11:15 |
| URI: | http://repo.dma.dp.ua/id/eprint/1934 |
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