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Trastuzumab biosimilar PF 05280014 non-inferior to Herceptin Posted 15/03/2019

Results of a study of Pfizer’s trastuzumab biosimilar (PF 05280014) have shown that the biosimilar is non-inferior to the originator biological, Roche’s Herceptin (trastuzumab) [1].

Pfizer’s phase III REFLECTIONS B327 02 (NCT01989676) trial is a randomized, parallel-group, active-controlled, double-blind, multicentre, international study. The study was designed to compare the efficacy, safety, pharmacokinetics and immunogenicity of PF 05280014 versus EU-sourced originator trastuzumab (Roche’s Herceptin) with paclitaxel in female patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer in the first-line treatment setting. The study is planned to be completed in June 2020.

A total of 707 subjects were randomized 1:1 to receive PF 05280014 (n = 352) or trastuzumab‑EU (n = 355). The primary endpoint was objective response rate (ORR) at Week 25, and confirmed at Week 33, defined as the percentage of subjects achieving complete response (CR) or partial response (PR), based on blinded central radiology review.

The risk ratio for ORR by Week 25 (confirmed by Week 33) in the intention-to-treat (ITT) population was 0.940 (PF 05280014 group over trastuzumab-EU group), with a 95% CI of 0.842‒1.049. Hence, the pre-specified definition of similarity between PF-05280014 and trastuzumab-EU was met. ORR was 62.5% (95% CI: 57.2‒67.6%) in the PF 05280014 group and 66.5% (95% CI: 61.3‒71.4%) in the trastuzumab-EU group.

As of data cut-off on 11 January 2017 (using data up to 378 days post-randomization), there were no notable differences between groups in progression-free survival (median: 12.16 months in the PF 05280014 group vs 12.06 months in the trastuzumab-EU group; 1-year rate: 54% vs 51%) or overall survival (median: not reached in either group; 1-year rate: 89.31% vs 87.36%). Safety outcomes and immunogenicity were similar between the treatment groups.

The results were published in the British Journal of Cancer (BJC).

The authors therefore concluded that ‘when given as first-line treatment for HER2-positive metastatic breast cancer, PF-05280014 plus paclitaxel demonstrated equivalence to trastuzumab-EU plus paclitaxel in terms of ORR’. They added that ‘as part of the totality of the evidence for assessing biosimilarity, these results are consistent with, and build upon, earlier analytical, non-clinical and clinical comparisons of PF 05280014 and reference trastuzumab’.

Pfizer’s trastuzumab biosimilar, Trazimera (PF 05280014), was approved in Europe in July 2018 [2] and in Japan in September 2018 [3]. It was, however, rejected by the US Food and Drug Administration (FDA) in April 2018 [4].

Conflict of interest
Several of the authors of the research paper [1] reported conflict of interest, including having consulted for, received research funding from, been a member of the speakers bureau for, received grants from, being employees of, or holding stocks in various pharmaceutical companies. For full details of the authors’ conflict of interest, see the research paper [1].

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References
1. Pegram MD, Bondarenko I, Zorzetto MMC, et al. PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study. Br J Cancer. 2019;120(2):172-82.
2. GaBI Online - Generics and Biosimilars Initiative. Adalimumab and trastuzumab biosimilars gain EC approval [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Mar 15]. Available from: www.gabionline.net/Biosimilars/News/Adalimumab-and-trastuzumab-biosimilars-gain-EC-approval 
3. GaBI Online - Generics and Biosimilars Initiative. Originator biologicals and biosimilars under attack in UK and Japan [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Mar 15]. Available from: www.gabionline.net/Biosimilars/General/Originator-biologicals-and-biosimilars-under-attack-in-UK-and-Japan
4. GaBI Online - Generics and Biosimilars Initiative. FDA rejects trastuzumab and rituximab biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Mar 15]. Available from: www.gabionline.net/Biosimilars/News/FDA-rejects-trastuzumab-and-rituximab-biosimilars 

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