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.
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.
OncLive: How have biosimilars entered the breast cancer landscape?
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.
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.
Have biosimilars had an impact on clinical practice yet?
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.
How will you determine when to use the biosimilar over the original drug?
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.