Miles, David; Cameron, David; Bondarenko, Igor; Manzyuk, Lyudmila; Alcedo, Juan Carlos; Lopez, Roberto Ivan; Im, Seock-Ah; Canon, Jean-Luc; Shparyk, Yaroslav; Yardley, Denise A; Masuda, Norikazu; Ro, Jungsil; Denduluri, Neelima; Hubeaux, Stanislas; Quah, Cheng; Bais, Carlos; O¡¯Shaughnessy, Joyce
European journal of cancer (Oxford, England : 1990)
2017Jan ; 70 ( 2 ) :146-155.
PMID : 27817944
ÀúÀÚ »ó¼¼Á¤º¸
Miles, David -
Cameron, David -
Bondarenko, Igor -
Manzyuk, Lyudmila -
Alcedo, Juan Carlos -
Lopez, Roberto Ivan -
Im, Seock-Ah -
Canon, Jean-Luc -
Shparyk, Yaroslav -
Yardley, Denise A -
Masuda, Norikazu -
Ro, Jungsil -
Denduluri, Neelima -
Hubeaux, Stanislas -
Quah, Cheng -
Bais, Carlos -
O¡¯Shaughnessy, Joyce -
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/m(2) 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-A(high) populations.
RESULTS: Of 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-A(high) 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 ??: 25% versus 13%) and hypertension (all grades: 31% versus 13%; grade ??: 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. CI - Copyright ??2016. Published by Elsevier Ltd.
Adult; Aged; Angiogenesis Inhibitors/administration & dosage; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use; Bevacizumab/administration & dosage; Biomarkers, Tumor/metabolism; Breast Neoplasms/diagnosis/*drug therapy/metabolism; Disease-Free Survival; Double-Blind Method; Female; Humans; Middle Aged; Molecular Targeted Therapy/*methods; Paclitaxel/administration & dosage; Prospective Studies; Receptor, ErbB-2/metabolism; Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism; Young Adult
MESH
Adult, Aged, Angiogenesis Inhibitors/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, Bevacizumab/administration & dosage, Biomarkers, Tumor/metabolism, Breast Neoplasms/diagnosis/*drug therapy/metabolism, Disease-Free Survival, Double-Blind Method, Female, Humans, Middle Aged, Molecular Targeted Therapy/*methods, Paclitaxel/administration & dosage, Prospective Studies, Receptor, ErbB-2/metabolism, Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism, Young Adult
¸µÅ©