Hurvitz Shares Insight on Breaking the Barrier With Biosimilars

Sara A. Hurvitz, MD

Although filgrastim-sndz (Zarxio), a biosimilar for the G-CSF analog filgrastim (Neupogen), is the only biosimilar commonly used in oncology practice, several studies have confirmed the benefit of biosimilars for trastuzumab (Herceptin) that could potentially lead to their routine clinical use once the anti-HER2 agent comes off patent, explains Sara A. Hurvitz, MD.

MYL-1401O (Ogivri; trastuzumab-dkst), the only trastuzumab biosimilar approved by the FDA, has approved indications for HER2-positive patients with breast cancer or metastatic gastric or gastroesophageal junction adenocarcinoma, the same indications as trastuzumab. Genentech, the manufacturer of trastuzumab, holds an exclusive license for the metastatic gastric cancer indication; therefore, Mylan and Biocon, the developers of MYL-1401O, cannot market the drug for that purpose until the exclusive license expires.

Another biosimilar, SB3, mirrored trastuzumab’s biologic activity and pharmacokinetic equivalence when the two were compared in a randomized, phase III, double-blind multicenter study in patients with HER2-positive early breast cancer. Patients were randomized to SB3 or trastuzumab over the course of 8 cycles with concurrent chemotherapy followed by surgery and 10 subsequent cycles of the biosimilar or trastuzumab. Breast pathologic complete responses were 51.7% for SB3 and 42.0% for trastuzumab.1 Complete safety and survival data have yet to be reported.

OncLive: How have biosimilars entered the breast cancer landscape?

In an interview with OncLive, Hurvitz, director of the Breast Oncology Program, medical director of the Clinical Research Unit, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, discussed the development of biosimilars and their potential use in the breast cancer field.Hurvitz: Biosimilars are drugs that are similar to biologic agents that are already FDA approved, but they are a little bit different from generic drugs. Generic drugs are equivalent chemical structures. Biologic agents are very complicated, large, protein-based molecules developed in cell lines and cannot be exact replicas of one another. Biologic agents account for billions of dollars of spending in healthcare, and access to these agents is limited worldwide. Biosimilar agents have the advantage of being much less expensive and will hopefully allow better access to these drugs.

Have biosimilars had an impact on clinical practice yet?

How will you determine when to use the biosimilar over the original drug?

There are several biosimilars that that have been approved in Europe and the United States, including biosimilars for trastuzumab, bevacizumab (Avastin), and the GCSF filgrastim biosimilar. In the coming years, as biologics come off patent, in the next year or 2, we're likely to see the clinical use of these agents in the United States more as a routine practice.As of 2018, the only biosimilar we are generally using in the United States is the filgrastim biosimilar. My own patients have been converted to the biosimilar form of filgrastim. It is a more affordable version, and it has met the biosimilarity criteria required by the FDA. Trastuzumab and bevacizumab have been FDA approved, but the originator drug is not yet off patent, so they’re not available in the United States for clinical use. Moreover, there is pending litigation regarding the patent, so it may be a few years before we actually see clinical use of these drugs in the United States. The FDA will determine which indications the biosimilar has been approved for. The regulatory pathway required for biosimilar agents is very different from the regulatory pathway and level of evidence required for an originator to be approved. For biosimilars, a study may show its similarity [to biologic agents] in its pharmacokinetics, immunogenicity, and efficacy outcomes in early-stage breast cancer. The FDA may extrapolate that data if it has met the totality of evidence and allow it to be approved not only in early-stage breast cancer, but in metastatic breast cancer, lung cancer, and other indications. That is what the [FDA] did for trastuzumab and bevacizumab; they extrapolated the evidence that's been provided and approved it in different indications than in the one that led to its approval.

You presented a session on biosimilars at the 2018 AACR Annnual Meeting. Is there anything else from that talk you would like to emphasize?

It is a less expensive alternative than the biologic agents. It's important for us to consider cost as long as the drug appears to be similar for our patients. There are several trastuzumab biosimilars under development, many of which already have clinical trial results being presented. I would expect that more FDA approvals are going to be coming very soon. I also led a session at the meeting that looked at outcome disparities in patients who are treated with biologic agents. There was a really nice talk by Dr Katie Reeder-Hayes that looked at disparities based on race and ethnicity and how we might address that. Several other speakers, including Dr Christopher S. Lathan, presented on disparities in lung cancer outcomes and how to address that from a race perspective. Dr Justin E. Bekelman addressed how we might address this from a healthcare and Medicare perspective, how we might be able to negotiate with Centers for Medicare & Medicaid Services for fairer drug prices, so that we can make drugs more available to patients regardless of socioeconomic status or race.

We have really made huge strides in improving outcomes for patients with these targeted drugs, but a lot of patients are not getting them because of their socioeconomic or race status.

Pivot X, Bondarenko I, Dvorkin M, et. al. A randomized, double-blind, phase III study comparing SB3 (trastuzumab biosimilar) with originator trastuzumab in patients treated by neoadjuvant therapy for HER2-positive early breast cancer. J Clin Oncol. 2017;35(15):509. doi: 10.1200/JCO.2017.35.15_suppl.509.