Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer

Lammers, Philip E.; Dank, Magdolna; Masetti, Riccardo; Abbas, Richat; Hilton, Fiona; Coppola, Jennifer; Jacobs, Ira

doi:10.1038/s41416-018-0147-1

Cited by 53 publications

(75 citation statements)

References 28 publications

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“…Progression-free survival at 48 weeks was 44.7% and 44.3% for reference and biosimilar trastuzumab, respectively; overall survival was 85.1% and 89.1%, respectively; adverse events affected 94.7% and 98.6% of patients, respectively [40,41]. PF-05280014, another biosimilar of trastuzumab, was reported as having demonstrated equivalence in its primary endpoint in November of the past year; data from this study have not yet been presented [42]. Finally, biosimilar trastuzumab has been investigated only as a single agent, while trastuzumab plus pertuzumab is considered the standard of care.…”

Section: Biopharmaceuticals In Breast Cancermentioning

confidence: 99%

Emerging Biosimilars in Oncology: A Review

Lavanya

2018

Asian J Pharm Clin Res

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Biosimilars are the biological medicinal products that produce the therapeutic effects in the human body similar to that of inner biological molecule. Biopharmaceuticals consist of nucleic acids, amino acids, polysaccharides, or combination of all compounds. In India, the steps have been taken to manufacture biosimilars with the lowest cost and least side effects. Globally, India is one of the major developing countries in manufacturing and marketing of biosimilars. The application of biosimilar was rapidly growing in treating various disorders such as cancer, inflammatory disease, and cardiovascular diseases. For the approval of biosimilars, in vitro studies become the necessity for representing comparison to a standard biological in terms of quality for experimental studies indicating similar pharmacokinetics, efficacy, safety, and immunogenicity. Huminsulin was the first DNA-recombinant protein accepted by the US Food and Drug Administration (FDA) in 1982. As currently there are no FDA-approved biosimilars for treating breast cancer, many biologic antibodies are under investigation.

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Section: Biopharmaceuticals In Breast Cancermentioning

confidence: 99%

Emerging Biosimilars in Oncology: A Review

Lavanya

2018

Asian J Pharm Clin Res

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“…CPT-6 was previously assessed in studies using both settings, but this was due to small changes in the production process that required duplication of all the comparability exercises . 4 For PF-05280014, clinical equivalence was based on a study in the metastatic setting, which was reported at ESMO by Pegram et al 1 Lammers et al report on a second trial, 8 innovatively added into the development, which has also assessed PF-05280014 in the neoadjuvant setting. Paired with their earlier findings, this second trial may appear as the icing on the cake.…”

Section: Mainmentioning

confidence: 99%

“…8 The 47% and 50% pCR rates achieved by PF-05280014 and Herceptin, respectively, provide a stratified difference for pCR of -2.81% (95% CI -16.58%/10.96%) based on investigator assessment. These differences and the 95% CI values are in line with the reported values provided by other biosimilar competitors in the same setting (Table 1).…”

Section: Mainmentioning

confidence: 99%

“…[1][2][3][4][5] In this issue of the British Journal of Cancer, Lammers et al report evidence establishing another step towards the registration of PF-05280014, a trastuzumab biosimilar candidate developed by Pfizer. 1,[6][7][8] This significant trial has provided clinical efficacy results of this candidate in patients with early breast cancer, and insight into its pharmacokinetic (PK) non-inferiority.The development of a biosimilar drug requires the collation of extensive pre-clinical comparability studies to demonstrate similar structural, physicochemical, and functional biological characteristics with the referent medical product. 9,10 .…”

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confidence: 99%

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Can we establish a hierarchy among trastuzumab biosimilar candidates?

Pivot¹,

Petit²

2018

Br J Cancer

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The European patent for intravenous trastuzumab lapsed in 2017, and this stimulated research into a number of trastuzumab biosimilars. Quality assessment of their development and clinical results might enable establishment of a clinical hierarchy of these agents. This editorial will underline the key points for consideration when determining such an evaluation.British Journal of Cancer (2018) 119:263-265; https://doi.org/10.1038/s41416-018-0171-1 MAINThe extraordinary clinical achievements of trastuzumab have made history in the systemic management of breast cancer. Unfortunately, it is not uniformly available for routine use owing to its prohibitively high cost. With financial contingencies following the economic crisis together with rapidly increasing healthcare costs, even the richest countries are exploring ways to reduce their healthcare expenditures. In 2017, the patent for intravenous trastuzumab (Herceptin) expired across Europe, which stimulated the development of numerous trastuzumab biosimilar agents (Table 1). [1][2][3][4][5] In this issue of the British Journal of Cancer, Lammers et al. report evidence establishing another step towards the registration of PF-05280014, a trastuzumab biosimilar candidate developed by Pfizer. 1,[6][7][8] This significant trial has provided clinical efficacy results of this candidate in patients with early breast cancer, and insight into its pharmacokinetic (PK) non-inferiority.The development of a biosimilar drug requires the collation of extensive pre-clinical comparability studies to demonstrate similar structural, physicochemical, and functional biological characteristics with the referent medical product. 9,10 . PK comparability in animal models is required prior to the first in-human study, and this is usually aimed at demonstrating PK equivalence between the biosimilar candidate and the referent. These steps have already been successfully achieved for PF-05280014.6,7 Treatment with trastuzumab can result in the production of anti-trastuzumab antibodies; therefore, initial phase I trials for PK assessment include healthy male subjects, because they are less likely to require treatment with trastuzumab for breast cancer in the future. Notably, several previous studies have validated the absence of observable discrepancies in PK profiles for trastuzumab between healthy volunteers and patients. 2,4,11,12 Iterative drug administration causes an accumulation of plasma drug levels, thus resulting in an increase of the average AUC (0-t) . For trastuzumab exposure, large variability in the AUC (0-t) is observed up to cycle 5, beyond which the values become stable and homogeneous over time. 13,14 Therefore, a large randomised study aimed at comparing the activities should also perform a PK assessment in patients receiving iterative administration.A randomised clinical study represents the ultimate step in the path towards drug registration, with the intention of providing evidence for similar efficacy between the biosimilar candidate and the reference medical product in a...

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“…CT-P6 (Herzuma®, Celltrion Healthcare, Incheon, ROK/Teva Pharmaceuticals, Petach Tikwa, Israel) and PF-05280014 (Trazimera®, Pfizer, New York, NY, USA/Hospira, Lake Forest, IL, USA) were evaluated in both mBC and eBC [14,15,16,17], ABP 980 (Kanjinti®, Amgen, Thousand Oaks, CA, USA) [18] and SB3 (Ontruzant®, Samsung Bioepis, Incheon, ROK/Daewoong Pharmaceuticals, Seoul, ROK/Merck (MSD), Kenilworth, NJ, USA) [19,20] only in eBC, and MYL-1410 (Ogivri®, Biocon, Bangalore, India/ Mylan, Canonsburg, PA, USA) [21] and BCD-022 (HERtiCAD®, Biocad, Saint Petersburg, Russia) only in mBC (NCT01764022). All biosimilars were evaluated with the recommended equivalence trial design, except for BCD-022 which was evaluated in a non-inferiority trial.…”

Section: Clinical Trials For Biosimilar Trastuzumabmentioning

confidence: 99%

Biosimilar Trastuzumab in Clinical Trials: Differences or Not?

Thill

2019

Breast Care

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In the last decade, cancer therapies have increasingly taken the form of combination treatments in which biologic agents play a crucial role. In breast cancer, the treatment strategy is adjusted to intrinsic subtypes such as human epidermal growth factor receptor-2(HER2)-positive. With the introduction of trastuzumab, a monoclonal antibody against HER2, survival has significantly improved in early and metastatic breast cancer. Trastuzumab's patent has now expired and biosimilars are moving into the market. Several clinical trials have led to the approval of 5 different biosimilar trastuzumabs. Results proved similarity between the proposed biosimilar and the reference product without significant differences in efficacy and safety, although follow-up has been short. However, the shorter drug development process with its goal of showing similarity rather than patient benefit uses surrogate endpoints such as pathologic complete response and overall response rate, not survival endpoints in terms of the ‘gold standard' in evaluating cancer therapies. The aim of this article is to give insight into how to plan and perform a clinical trial to prove equivalence between a biosimilar trastuzumab and its reference product and to elucidate the setup and outcome of published clinical trials.

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Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer

Abstract: PF-05280014 demonstrated non-inferior pharmacokinetics and comparable efficacy, safety and immunogenicity to trastuzumab-EU in patients with operable HER2-positive breast cancer receiving neoadjuvant chemotherapy.

Cited by 53 publications

References 28 publications

Emerging Biosimilars in Oncology: A Review

Emerging Biosimilars in Oncology: A Review

Can we establish a hierarchy among trastuzumab biosimilar candidates?

Biosimilar Trastuzumab in Clinical Trials: Differences or Not?

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