Reinmuth, Niels and Bryl, Maciej and Bondarenko, Igor and Syrigos, Kostas and Vladimirov, Vladimir and Zereu, Manuela and Bair, Angel H. and Hilton, Fiona and Liau, Katherine and Kasahara, Kazuo (2019) PF‑06439535 (a Bevacizumab Biosimilar) Compared with Reference Bevacizumab (Avastin®), Both Plus Paclitaxel and Carboplatin, as First‑Line Treatment for Advanced Non‑Squamous Non‑Small‑Cell Lung Cancer: A Randomized, Double‑Blind Study. BioDrugs. pp. 1-16. ISSN 1173-8804 (Print) 1179-190X (Online)
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Abstract
Background PF-06439535 is a bevacizumab biosimilar. We aimed to compare the efcacy and safety of PF-06439535 with that of reference bevacizumab (Avastin®) sourced from the EU (bevacizumab-EU), each with paclitaxel and carboplatin, in the frst-line treatment of advanced non-squamous non-small-cell lung cancer (NSCLC). Methods In this double-blind, parallel-group study, we recruited patients from 159 centers in 27 countries. Participants were randomized 1:1 to receive PF-06439535 plus paclitaxel and carboplatin or bevacizumab-EU plus paclitaxel and carboplatin on day 1 of each 21-day cycle for 4–6 cycles, followed by blinded monotherapy with PF-06439535 or bevacizumab-EU until disease progression, unacceptable toxicity, withdrawal of consent, or the end of the study. Randomization was stratifed by region, sex, and smoking history. The primary endpoint was objective response rate (ORR) in accordance with RECIST 1.1, based on responses achieved by week 19 and confrmed by week 25. Results Between 21 May 2015 and 14 November 2016, 719 patients were randomized to the PF-06439535 group (n = 358) or the bevacizumab-EU group (n = 361). As of data cutof for analysis of the primary endpoint (8 May 2017), 45.3% (95% confdence interval [CI] 40.01–50.57) of patients in the PF-06439535 group and 44.6% (95% CI 39.40–49.89) of patients in the bevacizumab-EU group achieved an objective response by week 19 that was confrmed by week 25. The unstratifed ORR risk ratio was 1.015 (95% CI 0.863–1.193; 90% CI 0.886–1.163), and the unstratifed ORR risk diference was 0.653% (95% CI −6.608 to 7.908); all three CIs fell within pre-specifed equivalence margins. Using fnal data after study completion (22 December 2017), no notable diferences in progression-free survival or overall survival were observed between the groups. The most frequently reported grade 3 or higher treatment-emergent adverse events were hypertension, neutropenia, and anemia. There were no clinically meaningful diferences in safety, pharmacokinetics, or immunogenicity across treatment groups. Conclusion Among patients with advanced non-squamous NSCLC, PF-06439535 demonstrated similarity to bevacizumabEU in terms of efcacy. Safety profles for the two treatments were comparable. Trial Registration ClinicalTrials.gov, NCT02364999. Funding Pfzer.
| Item Type: | Article |
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| Additional Information: | https://doi.org/10.1007/s40259-019-00363-4 |
| Subjects: | Oncology |
| Divisions: | Departments > Department of Oncology and Medical Radiology |
| Depositing User: | Елена Шрамко |
| Date Deposited: | 11 Oct 2019 10:56 |
| Last Modified: | 11 Oct 2019 10:56 |
| URI: | http://repo.dma.dp.ua/id/eprint/4358 |
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