Lee S. Schwartzberg, MD
Results of a retrospective analysis demonstrated statistical significance in the incidence of febrile neutropenia between patients with nonmyeloid cancer who received a filgrastim (Neupogen) biosimilar (Zarxio; biosimilar filgrastim-sndz) versus the filgrastim biologic (filgrastim-ref) during their first chemotherapy cycle, explained lead author Lee Schwartzberg, MD.
Included in the study were those who were enrolled in commercial or Medicare Advantage insurance plans from March 2015 through June 2016 and received either filgrastim-sndz or filgrastim-ref. After adjusting for differences in baseline patient characteristics using the inverse probability of treatment-weighting method, there were 162 patients in the filgrastim-sndz cohort and 3297 in the filgrastim-ref cohort.
Febrile neutropenia was defined by neutropenia and fever (N/F), neutropenia and infection (N/I), and neutropenia, infection, and fever (N/I/F). The incidences of febrile neutropenia were 1.4% versus 0.9% for N/F, 2.3% versus 1.7% for N/I, and 0.0% versus 0.3% for N/I/F in the respective filgrastim-sndz and filgrastim-ref cohorts.
In March 2015, the FDA approved filgrastim-sndz as the first biosimilar approved in the United States. The agent was approved for all 5 indications of filgrastim. In July 2018, the FDA approved a second filgrastim biosimilar, filgrastim-aafi (Nivestym) for the same indications.
“The use of biosimilars is poised to explode in the United States oncology market because they work as well as the originator product, and they're less expensive,” said Schwartzberg, a medical oncologist and hematologist at West Cancer Center.
In an interview with OncLive®
, Schwartzberg elaborated on the retrospective analysis and discussed how biosimilars have the potential to transform the field of oncology beyond the scope of supportive care.
OncLive: What was the rationale behind the retrospective analysis?
: The reason to do the study was to look at real-world evidence that accumulated after the introduction of a filgrastim biosimilar in the United States. We wanted to see if the real-world data replicated what was seen in the clinical trials [in patients who experienced febrile neutropenia]. Specifically, we wanted to see if the clinical outcomes, that is febrile neutropenia–associated outcomes were similar [between products] and assess the cost associated with febrile neutropenia in a real-world cohort [of patients].
Based on the findings of the study, were the clinical trial results reflected in the real-world cohort?
Yes. We found that there was no difference, statistically, between the incidences of febrile neutropenia—defined a couple of different ways—between the group that received filgrastim-sndz versus the standard originator filgrastim. The incidence of febrile neutropenia was low in both groups. We defined febrile neutropenia based on a sample from a managed care population that was a billing claims analysis sample. Using a variety of techniques to both assess the claims and to adjust for differences between the populations using propensity scores, we were able to see there was no difference.
What about the associated costs?
The costs were in line with what others have reported. The costs for an episode of febrile neutropenia, which are fairly expensive, ranged from about $12,000 up to $22,000 depending on the definition we used. Most of the costs were driven by hospitalization. Most patients in our sample who had febrile neutropenia and infection as documented by the claims were admitted to the hospital. In fact, 70% of those patients were admitted. That reflects the standard across the United States. When patients have clinical neutropenia and a documented infection, or even just febrile neutropenia, they still have a high chance of being admitted.
Are you using the filgrastim biosimilar in practice?
In my practice, we use the filgrastim biosimilar. It's our filgrastim of choice. It's less expensive than the originator drug, and it works just as well. The study showed that just like in the clinical trials, there is no meaningful difference clinically between the biosimilar filgrastim and the standard filgrastim when used for prophylaxis, or for any other likely cause.
What does the study mean in the larger context of biosimilars in oncology?
We all know that the cost of healthcare, and specifically the cost of cancer care, is skyrocketing. For a while, we have been trying to bend the curve with varying levels of success in terms of the ever-increasing cost of cancer care. One of the ways to do that is to find drugs with equal efficacy and less cost. Biosimilars fit that criteria. Biosimilars have been heavily vetted by the FDA. There's a different but rigorous pathway towards approval of a biosimilar that the FDA has now signed off on and is increasingly utilizing to approve additional biosimilars.
I believe that the uptake of biosimilars has been fairly enthusiastic in the United States. We lag a few years behind, namely because of administrative regulatory issues. In other words, the FDA has to finalize the process by which biosimilars can be approved. Europe has been doing it for longer, and they have a tremendous amount of experience with biosimilars with very good outcomes. We'll be seeing biosimilars coming for most of the biologics that are out there.
Of course, you can't market a biosimilar until the patent on the originator product is expired. Some of those will be expiring on some of the common drugs we've been using in cancer care, not only for supportive care drugs, such as filgrastim, but also therapeutically. We already have a rituximab (Rituxan) biosimilar, and we'll have trastuzumab (Herceptin) and bevacizumab (Avastin) in the near future. The use of biosimilars is poised to explode in the United States oncology market because they work as well as the originator product, and they're less expensive. I'd like to see even more cost differential, but we'll have to see how that plays out in the marketplace.
Are there added incentives to use a biosimilar over an originator biologic?
In the free marketplace, the cost of drugs is fluid and is influenced by various factors, including market share, volume, and so forth. In general, biosimilars are trying to come in at a lower average wholesale acquisition cost than the originator product.
Following the second filgrastim biosimilar approval, how do you select which one to use?
If we believe that biosimilars are equally effective, [it] becomes a decision based on not only the cost of the product but the customer service given by the manufacturer for the product.
Where do you see the field of biosimilars headed?
Right now, our experience has been mainly in supportive care. Many physicians will take increased scrutiny of the clinical data when it comes to using biosimilars in a therapeutic fashion. There's no reason to believe that they shouldn't work in the therapeutic setting for the treatment of cancer, even in the curative treatment of cancer, than they do in the supportive care arena. They have been investigated in clinical trials to prove that they're clinically nondifferent from the originator product in those settings, as well.
Schwartzberg L, Lal L, Balu S, et al. Clinical outcomes of treatment with filgrastim versus filgrastim biosimilar and febrile-neutropenia-associated costs among patients with nonmyeloid cancer undergoing chemotherapy [published online ahead of print April 24, 2018]. J Manag Care Spec Pharm. doi: 10.18553/jmcp.2018.17447.