Safety and immunogenicity of originator and biosimilar trastuzumab

Biosimilars/Research | Posted 24/08/2018 post-comment0 Post your comment

A study carried out by international researchers reported results from the HERiTAge trial of Mylan/Biocon’s biosimilar trastuzumab, Ogivri (trastuzumab‑dkst) [1].

Health and Safety V15C26

Mylan/Biocon’s Ogivri (trastuzumab‑dkst) was approved in the US in December 2017 [2]. US approval was based on results from the phase III HERiTAge study. The multicentre, double-blind, randomized, parallel-group, phase III equivalence study was carried out between 2012 and 2015. It included 500 women with HER2+ metastatic breast cancer without prior treatment for metastatic disease [3].

The HERiTAge trial evaluated the efficacy and safety of Ogivri vs trastuzumab, in combination with taxane as first-line therapy for patients with HER2+ metastatic breast cancer. The primary endpoint was overall response rate on combination therapy at Week 24 and has been previously reported [3].

Eligible patients were randomized 1:1 to receive trastuzumab-dkst or originator trastuzumab, combined with taxane. After 24 weeks, patients with responding or stable disease received monotherapy as per randomization.

The authors report the results of the secondary endpoints of safety and immunogenicity during monotherapy and cumulative through 48 weeks. A total of 500 patients were randomized, 342 continued treatment after 24 weeks and 214 continued through 48 weeks. Treatment-emergent adverse event (TEAE) rates during monotherapy were similar (trastuzumab-dkst, 54.7%; trastuzumab, 60.1%); most were low grade. Grade ≥3 TEAEs were more frequent with trastuzumab (11.7%) vs trastuzumab-dkst (6.7%); serious TEAE rates were similar (trastuzumab-dkst, 2.8%; trastuzumab, 2.5%). When assessed over 48 weeks of combination and monotherapy, cumulative rates of TEAEs of special interest were similar for pulmonary events, significant cardiac disorders, and infusion-related events (trastuzumab-dkst, 13.0%, 4.9%, and 9.3%; trastuzumab, 12.2%, 4.1%, and 8.1%, respectively). Immunogenicity and incidence of left ventricular ejection fraction < 50% ≥ 1 time postbaseline and ≥ 10% reduction at Week 48 were similar between groups (trastuzumab-dkst, 3.9% and 3.6%; trastuzumab, 4.4% and 2.8%, respectively). No new safety signals were detected. At Week 48, median progression-free survival (PFS) was 11.1 months in both groups and overall survival (OS) curves were similar.

These data were presented at the American Society of Clinical Oncology’s (ASCO) 2018 Annual Meeting, which was held on 1−5 June 2018 in Chicago, IL, USA.

The authors concluded that ‘maintenance monotherapy with FDA-approved trastuzumab-dkst after combination with taxane was well tolerated, with safety and efficacy profiles similar to originator trastuzumab’.

Conflict of interest
The authors of the abstract [1] declared that there were no conflicts of interest.

Editor’s comment
It should be noted that data of the study presented in this article was published as an abstract and presented at a conference. These data and conclusions should be considered as preliminary until published in a peer-reviewed journal.

Related article
Mylan presents comparability data for trastuzumab biosimilar

1.  Manikhas A, Pennella EJ, Bondarenko I, et al. Biosimilar trastuzumab-dkst monotherapy versus trastuzumab monotherapy after combination therapy: Toxicity, efficacy, and immunogenicity from the phase 3 Heritage trial. American Society of Clinical Oncology (ASCO) 2018 Annual Meeting; 1-5 June 2018; Chicago IL, USA.
2. GaBI Online - Generics and Biosimilars Initiative. FDA approves trastuzumab biosimilar Ogivri []. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Aug 24]. Available from:
3. GaBI Online - Generics and Biosimilars Initiative. Candidate trastuzumab biosimilar meets equivalence requirements []. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Aug 24]. Available from:

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