Phase 3 and Postmarketing Data Support the Efficacy and Safety of Biosimilar Trastuzumab, Ogivri

Mylan and Biocon’s trastuzumab biosimilar, Ogivri, was the first biosimilar referencing Herceptin to be approved by the FDA. Approval of Ogivri was based in part on data from the phase 3 HERITAGE trial, a double-blind, randomized clinical trial that evaluated the biosimilar in patients with HER2-positive metastatic breast cancer without prior chemotherapy or trastuzumab for metastatic disease.

Data from the HERITAGE study, reported elsewhere, show that the biosimilar was equivalent to the reference trastuzumab when giving in combination with a taxane as first-line therapy, as measured by 24-week overall response. The safety profile of the biosimilar was also comparable to that of the reference Herceptin.¹

During this week’s 2019 American Society of Clinical Oncology Annual Meeting, researchers presented the final overall survival (OS) results from HERITAGE.²

After 24 weeks, the 343 patients who had responding or stable disease continued to receive trastuzumab as monotherapy according to their initial randomization to either the biosimilar (n = 179) or the reference (n = 164). Safety and OS during maintenance, through 36 months of follow-up from the last patient on the study, were included in the results.

The mean time to discontinuation was 19 months in both the biosimilar arm and the reference arm. Treatment-emergent adverse events (AEs) during monotherapy were similar in the biosimilar arm (69%) and the reference arm (73%). Serious AEs occurred in 6% of patients in both groups.

At 36 months, 169 patients had received additional lines of therapy, with a similar distribution of HER2 treatments, endocrine therapies, and chemotherapies.

Final median progression-free survival was 11.1 months in both of the arms. The median duration of response was 9.9 months in the biosimilar arm and 9.8 months in the reference arm. OS was 35.0 months and 30.2 months in the 2 arms, respectively.

In addition to these data from HERITAGE, separately, another research group shared its research on postmarketing surveillance of Ogivri, and said that their results show that the safety of the biosimilar is consistent with that of the reference.³

The biosimilar, while not yet launched in the United States, is available in other markets, including Brazil, where it is subject to a manufacturer-supported patient support program that monitors AEs. The authors of a prospective observational study used data from the program that covered 21 patients with HER2-positive breast cancer who enrolled in the program between May 2018 and January 2019.

In total, 16 patients reported 101 AEs, 7 of which were serious. The most frequently reported AEs were general disorders and administration-site conditions, followed by nervous system disorders and gastrointestinal disorders. The most-reported symptoms were nausea, asthenia, infusion-site reactions, paresthesia, and pain.

According to the investigators, these safety data are consistent with the profile of the reference trastuzumab, and no new safety signals were detected.

References

1. Rugo H, Barve A, Waller C, et al. HERITAGE: a phase III safety and efficacy trial of the proposed trastuzumab biosimilar Myl-1401O versus Herceptin. Eur J Cancer. 2017;72(1):S41. doi: 10.1016/S0959-8049(17)30216-2.

2. Waller CF, Manikhas A, Penella EJ, et al. Biosimilar trastuzumab-dkst monotherapy versus trastuzumab monotherapy after combination therapy: final overall survival (OS) from the phase III HERITAGE Trial. Presented at: American Society of Clinical Oncology Annual Meeting 2019; May 31-June 4, 2019; Chicago, Illinois. Abstract 1021.

3. da Silva AM, Dib GVC, Saraiva ELF, Watanabe TT, de Paulo JA. Active postmarketing surveillance: Results from a manufacturer's patient support program for patients under treatment with the first biosimilar trastuzumab (MYL-1401O) approved in Brazil. Presented at: American Society of Clinical Oncology Annual Meeting 2019; May 31-June 4, 2019; Chicago, Illinois. Abstract e1400.